nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2021-25-6-9-15nefr-2045Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESЭпигенетические механизмы нефропротекции при диабетической нефропатии: в фокусе сиртуин-1Epigenetic mechanisms of nephroprotection in diabetic nephropathy: focus is on sirtuin-1https://orcid.org/0000-0003-4973-039XАйтбаевК. А.AitbaevK. A.

Айтбаев Кубаныч Авенович - доктор медицинских наук, проф. руководитель отдела патологической физиологии. Член правления Общества специалистов по хронической болезни почек Кыргызстана.

720040, Бишкек, ул. Т. Молдо, д. 3, Тел.: (312) 66-25-13

Prof. Kubanych A. Aitbaev - Research Institute of Molecular Biology and Medicine at the National Center for Cardiology and Therapy named after academician Mirsaid Mirrakhimov, Head of the Department of Pathological Physiology. Member of the Board of the Society of Chronic Kidney Disease Specialists of Kyrgyzstan.

MD, PhD, DMedSci 720040, Bishkek, T. Moldo, Street, 3. Phone: (312) 66-25-13

kaitbaev@yahoo.comhttps://orcid.org/0000-0001-8513-9279МуркамиловИ. Т.MurkamilovI. T.

Муркамилов Илхом Торобекович - кандидат медицинских наук, Исполняющий обязанности доцента кафедры факультетской терапии Кыргызской ГМА; старший преподаватель кафедры терапии №2 медицинского факультета Кыргызско-Российского славянского университета. Председатель правления Общества специалистов по хронической болезни почек Кыргызстана.

720020, Бишкек, ул. Ахунбаева, д. 92. Тел.: (312) 62-09-91

Ilkhom T. Murkamilov - MD, PhD, acting associate professor of the Department of faculty therapy of Kyrgyz SMA named after I.K. Akhunbaev, Senior lecturer of Kyrgyz-Russian SU. Chairman of the board of Chronic Kidney Disease specialists Society of Kyrgyzstan.

720020, Bishkek, Akhunbaev Street, 92. Phone: (312) 62-09-91

murkamilov.i@mail.ruhttps://orcid.org/0000-0002-2682-4417ФоминВ. В.FominV. V.

Фомин Виктор Викторович - доктор медицинских наук профессор, Чл.-кор. РАН, Заведующий кафедрой факультетской терапии №1 Института клинической медицины имени Н.В. Склифосовского, проректор по клинической работе и дополнительному профессиональному образованию, ФГАОУ ВО Первый МГМУ имени И.М. Сеченова (Сеченовский Университет).

119146, Москва, ул. Большая Пироговская, д. 6. Тел.: 8 (499) 248-62-22

Сorresponding member of RAS Viktor V. Fomin - MD, PhD. DMedSci, professor Head of the Department of Faculty Therapy No.1 of the Sklifos-ovsky Institute, Vice-rector in clinical work and continuous professional education, I.M. Sechenov First Moscow SMU (Sechenov University).

119146, Moscow, 6 Bolshaya Pirogovskaya, Street 6. Phone: +7 (499) 248-62-22

fomin@mma.ruhttps://orcid.org/0000-0002-7653-0433МуркамиловаЖ. А.MurkamilovaZh. A.

Муркамилова Жамила Абдилалимовна - заочный аспирант, Кафедра терапии №2 медицинского факультета.

720000, Кыргызстан, Бишкек, ул. Киевская, д. 44. Тел.: (+996) 552435009

Correspondence graduate student Zhamila A. Murkamilova – Department of Therapy No. 2 of the Medical Faculty, SEI HPE Kyrgyz-Russian SU.

720000, Bishkek, Kiev, Street, 44. Phone: (+996) 552435009

murkamilov.i@mail.ruhttps://orcid.org/0000-0003-0632-6653ЮсуповФ. А.YusupovF. A.

Проф. Юсупов Фуркат Абдулахатович - доктор медицинских наук, заведующий кафедрой неврологии, психиатрии и нейрохирургии медицинского факультета Ошского ГУ, Член правления Общества специалистов по хронической болезни почек Кыргызстана, главный невролог Южного региона Кыргызстана.

714000, Ош, ул. Ленина, д. 331. Тел.: (+996) 557202071

Prof. Furkat A. Yusupov - MD, PhD. Head of the Department of neurology, psychiatry and medicinal genetics of medicinal faculty of Osh State University. Board member of Chronic Kidney Disease specialists Society of Kyrgyzstan, Chief neurologist of Southern region of Kyrgyzstan.

714000, Osh, Lenin Street, 331. Phone: (+996) 557202071

furcat_y@mail.ruНИИ молекулярной биологии и медицины, Национальный центр кардиологии и терапии имени академика Мирсаида МиррахимоваКазахстанResearch Institute of Molecular Biology and MedicineKazakhstanКыргызская государственная медицинская академия им. И. К. АхунбаеваКыргызстанI.K. Akhunbaev Kyrgyz State Medical AcademyKyrgyzstanИнститут клинической медицины имени Н.В. Склифосовского, Первый Московский государственный медицинский университет имени И. М. СеченоваРоссияSklifosovsky Institute, I.M. Sechenov First Moscow State Medical UniversityRussian FederationКыргызско-Российский славянский университетКыргызстанKyrgyz Russian Slavic UniversityKyrgyzstanОшский государственный университетКыргызстанOsh State UniversityKyrgyzstan202117112021256915Copyright © Айтбаев К.А., Муркамилов И.Т., Фомин В.В., Муркамилова Ж.А., Юсупов Ф.А., 20212021Айтбаев К.А., Муркамилов И.Т., Фомин В.В., Муркамилова Ж.А., Юсупов Ф.А.Aitbaev K.A., Murkamilov I.T., Fomin V.V., Murkamilova Z.A., Yusupov F.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/2045

Многочисленными исследованиями показана критическая роль деацетилазы сиртуина-1 (SIRT1) в защите почечных клеток от эндогенных и экзогенных стрессов. Защитная роль SIRT1 была установлена как в подоцитах, так и в клетках почечных канальцев при многих заболеваниях почек, включая диабетическую нефропатию (ДН). Показано также, что SIRT1 оказывает нефропротективные эффекты при ДН отчасти через деацетилирование факторов транскрипции, участвующих в патогенезе заболевания, таких как p53, FOXO, RelA / p65NF-KB, STAT3 и PGC1a / PPARy. Недавно установлено, что специфическая для подоцитов избыточная экспрессия SIRT1 ослабляет протеинурию и повреждение почек на экспериментальной модели ДН, что свидетельствует о возможности использования SIRT1 в качестве потенциальной мишени для лечения заболеваний почек. Кроме того, агонисты SIRT1, такие как ресвера-трол и BF175, уменьшали диабетическое повреждение почек на нескольких экспериментальных моделях животных. Также удалось показать, что пуэрарин, китайское растительное лекарственное средство, активирует SIRT1, обеспечивая нефропротекцию на мышиной модели ДН. Помимо агонистов SIRT1, нефропротективный эффект оказывают и ингибиторы бромодомена, в частности MS417. Эти результаты свидетельствуют о том, что агонисты SIRT1 и ингибиторы бромодомена могут быть новыми потенциальными терапевтическими средствами, замедляющими прогрессирование ДН.

Numerous studies have shown the critical role of sirtuin-1 deacetylase (SIRT1) in the protection of renal cells from endogenous and exogenous stresses. A protective role for SIRT1 has been established in both podocytes and renal tubular cells in many kidney diseases, including diabetic nephropathy (DN). SIRT1 has also been shown to have nephroprotective effects in DN, in part through the deacetylation of transcription factors involved in disease pathogenesis, such as p53, FOXO, RelA / p65NF-KB, STAT3, and PGC1a / PPARy. Recently, it was found that podocyte-specific overexpression of SIRT1 attenuates proteinuria and kidney damage in an experimental model of DN, suggesting the possibility of using SIRT1 as a potential target for the treatment of kidney disease. In addition, SIRT1 agonists such as resveratrol and BF175 have been shown to reduce diabetic kidney damage in several experimental animal models. It has also been shown that puerarin, a Chinese herbal medicine, activates SIRT1, providing nephroprotection in a mouse model of DN. In addition to SIRT1 agonists, inhibitors of bromodomain, in particular, MS417, also have a nephroprotective effect. These results suggest that SIRT1 agonists and bromodomain inhibitors may be new potential therapeutic agents that slow the progression of DN.

SIRT1ацетилированиедиабетическая нефропатияингибитор бромодоменаподоцитыSIRT1acetylationdiabetic nephropathybromodomain inhibitorpodocytesReferencesMoynihan KA, Grimm AA, Plueger MM et al. Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metab 2005; 2:105-117. https://doi.org/10.1016/j.cmet.2005.07.001Moynihan KA, Grimm AA, Plueger MM et al. Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metab 2005; 2:105-117. https://doi.org/10.1016/j.cmet.2005.07.001Rodgers JT, Lerin C, Haas W et al. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2005; 434:113-118. https://doi.org/10.1038/nature03354Rodgers JT, Lerin C, Haas W et al. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2005; 434:113-118. https://doi.org/10.1038/nature03354Salminen A, Kaarniranta K. SIRT1: regulation of longevity via autophagy. Cell Signal 2009; 21:1356-1360. https://doi.org/10.1016/j.cellsig.2009.02.014Salminen A, Kaarniranta K. SIRT1: regulation of longevity via autophagy. Cell Signal 2009; 21:1356-1360. https://doi.org/10.1016/j.cellsig.2009.02.014Scarpulla RC. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta 2011; 1813:1269-1278. https://doi.org/10.1016/j.bbamcr.2010.09.019Scarpulla RC. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta 2011; 1813:1269-1278. https://doi.org/10.1016/j.bbamcr.2010.09.019Luo J, Nikolaev AX Imai S et al. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 2001; 107:137-148. https://doi.org/10.1016/S0092-8674(01)00524-4Luo J, Nikolaev AX Imai S et al. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 2001; 107:137-148. https://doi.org/10.1016/S0092-8674(01)00524-4Hasegawa K, Wakino S, Yoshioka K et al. Kidney-specific overexpression of SIRT1 protects against acute kidney injury by retaining peroxisome function. J Biol Chem 2010; 285:13045-13056. https://doi.org/10.1074/jbc.M109.067728Hasegawa K, Wakino S, Yoshioka K et al. Kidney-specific overexpression of SIRT1 protects against acute kidney injury by retaining peroxisome function. J Biol Chem 2010; 285:13045-13056. https://doi.org/10.1074/jbc.M109.067728He W, Wang X Zhang MZ et al. SIRT1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest 2010; 120:1056-1068. https://doi.org/10.1172/JCI41563He W, Wang X Zhang MZ et al. SIRT1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest 2010; 120:1056-1068. https://doi.org/10.1172/JCI41563Kume S, Uzu T, Horiike K et al. Calorie restriction enhances cell adaptation to hypoxia through SIRT1- dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 2010; 120:10431055. https://doi.org/10.1172/JCI41376Kume S, Uzu T, Horiike K et al. Calorie restriction enhances cell adaptation to hypoxia through SIRT1- dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 2010; 120:10431055. https://doi.org/10.1172/JCI41376Nakagawa T, Guarente L. Sirtuins at a glance. J Cell Sci 2011; 124:833-838. https://doi.org/10.1242/jcs.081067Nakagawa T, Guarente L. Sirtuins at a glance. J Cell Sci 2011; 124:833-838. https://doi.org/10.1242/jcs.081067Vaziri H, Dessain SK, Ng Eaton E et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 2001; 107:149-159. https://doi.org/10.1016/S0092-8674(01)00527-XVaziri H, Dessain SK, Ng Eaton E et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 2001; 107:149-159. https://doi.org/10.1016/S0092-8674(01)00527-XJang SY, Kim SX Bae YS. p53 deacetylation by SIRT1 decreases during protein kinase CKII downregulation-mediated cellular senescence. FEBS Lett 2011; 585:3360-3366. https://doi.org/10.1016/j.febslet.2011.09.027Jang SY, Kim SX Bae YS. p53 deacetylation by SIRT1 decreases during protein kinase CKII downregulation-mediated cellular senescence. FEBS Lett 2011; 585:3360-3366. https://doi.org/10.1016/j.febslet.2011.09.027Milner J, Allison SJ. SIRT1, p53 and mitotic chromosomes. Cell Cycle 2011; 10:3049. https://doi.org/10.4161/cc.10.18.16994Milner J, Allison SJ. SIRT1, p53 and mitotic chromosomes. Cell Cycle 2011; 10:3049. https://doi.org/10.4161/cc.10.18.16994Shah ZH, Ahmed SU, Ford JR et al. A deacetylasedefi-cient SIRT1 variant opposes full-length SIRT1 in regulating tumor suppressor p53 and governs expression of cancer-related genes. Mol Cell Biol 2012; 32:704-716. https://doi.org/10.1128/MCB.06448-11Shah ZH, Ahmed SU, Ford JR et al. A deacetylasedefi-cient SIRT1 variant opposes full-length SIRT1 in regulating tumor suppressor p53 and governs expression of cancer-related genes. Mol Cell Biol 2012; 32:704-716. https://doi.org/10.1128/MCB.06448-11Brunet A, Sweeney LB, Sturgill JF et al. Stressdependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 2004; 303:2011-2015. https://doi.org/10.1126/science.1094637Brunet A, Sweeney LB, Sturgill JF et al. Stressdependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 2004; 303:2011-2015. https://doi.org/10.1126/science.1094637Motta MC, Divecha N, Lemieux M et al. Mammalian SIRT1 represses forkhead transcription factors. Cell 2004; 116:551-563. https://doi.org/10.1016/S0092-8674(04)00126-6Motta MC, Divecha N, Lemieux M et al. Mammalian SIRT1 represses forkhead transcription factors. Cell 2004; 116:551-563. https://doi.org/10.1016/S0092-8674(04)00126-6Chuang PX Yu Q, Fang W et al. Advanced glycation end-products induce podocyte apoptosis by activation of the FOXO4 transcription factor. Kidney Int 2007; 72:965-976. https://doi.org/10.1038/sj.ki.5002456Chuang PX Yu Q, Fang W et al. Advanced glycation end-products induce podocyte apoptosis by activation of the FOXO4 transcription factor. Kidney Int 2007; 72:965-976. https://doi.org/10.1038/sj.ki.5002456Chuang PX Dai X Liu R et al. Alteration of forkhead box O (foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus. PLoS ONE 2011; 6:e23566. https://doi.org/10.1371/journal.pone.0023566Chuang PX Dai X Liu R et al. Alteration of forkhead box O (foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus. PLoS ONE 2011; 6:e23566. https://doi.org/10.1371/journal.pone.0023566Bernier M, Paul RK, Martin-Montalvo A et al. Negative regulation of STAT3 protein-mediated cellular respiration by SIRT1 protein. J Biol Chem 2011; 286:19270-19279. https://doi.org/10.1074/jbc.M110.200311Bernier M, Paul RK, Martin-Montalvo A et al. Negative regulation of STAT3 protein-mediated cellular respiration by SIRT1 protein. J Biol Chem 2011; 286:19270-19279. https://doi.org/10.1074/jbc.M110.200311Nie X Erion DM, Yuan Z et al. STAT3 inhibition of glu-coneogenesis is downregulated by SIRT1. Nat Cell Biol 2009; 11:492-500. https://doi.org/10.1038/ncb1857Nie X Erion DM, Yuan Z et al. STAT3 inhibition of glu-coneogenesis is downregulated by SIRT1. Nat Cell Biol 2009; 11:492-500. https://doi.org/10.1038/ncb1857Sestito R, Madonna S, Scarponi C et al. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation. FASEB J 2011; 25:916-927. https://doi.org/10.1096/fj.10-172288Sestito R, Madonna S, Scarponi C et al. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation. FASEB J 2011; 25:916-927. https://doi.org/10.1096/fj.10-172288Schenk S, Mccurdy CE, Philp A et al. SIRT1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction. J Clin Invest 2011; 121:4281-4288. https://doi.org/10.1172/JCI58554Schenk S, Mccurdy CE, Philp A et al. SIRT1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction. J Clin Invest 2011; 121:4281-4288. https://doi.org/10.1172/JCI58554Chen L, Fischle W, Verdin E, Greene WC. Duration of nuclear NFkappaB action regulated by reversible acetylation. Science 2001; 293:1653-1657. https://doi.org/10.1126/science.1062374Chen L, Fischle W, Verdin E, Greene WC. Duration of nuclear NFkappaB action regulated by reversible acetylation. Science 2001; 293:1653-1657. https://doi.org/10.1126/science.1062374Greene WC, Chen LF. Regulation of NF-kappaB action by reversible acetylation. Novartis FoundSymp 2004; 259:208-217; discussion 218-225. https://doi.org/10.1002/0470862637.ch15Greene WC, Chen LF. Regulation of NF-kappaB action by reversible acetylation. Novartis FoundSymp 2004; 259:208-217; discussion 218-225. https://doi.org/10.1002/0470862637.ch15Yang XD, Tajkhorshid E, Chen LF. Functional interplay between acetylation and methylation of the RelA subunit of NF-kappaB. Mol Cell Biol 2010; 30:2170-2180. https://doi.org/10.1128/MCB.01343-09Yang XD, Tajkhorshid E, Chen LF. Functional interplay between acetylation and methylation of the RelA subunit of NF-kappaB. Mol Cell Biol 2010; 30:2170-2180. https://doi.org/10.1128/MCB.01343-09Geng H, Harvey CT, Pittsenbarger J et al. HDAC4 protein regulates HIF1alpha protein lysine acetylation and cancer cell response to hypoxia. J Biol Chem 2011; 286:38095-38102. https://doi.org/10.1074/jbc.M111.257055Geng H, Harvey CT, Pittsenbarger J et al. HDAC4 protein regulates HIF1alpha protein lysine acetylation and cancer cell response to hypoxia. J Biol Chem 2011; 286:38095-38102. https://doi.org/10.1074/jbc.M111.257055Lim JH, Lee YM, Chun YS et al. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell 2010; 38:864-878. https://doi.org/10.1016/j.molcel.2010.05.023Lim JH, Lee YM, Chun YS et al. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell 2010; 38:864-878. https://doi.org/10.1016/j.molcel.2010.05.023Chen R, Dioum EM, Hogg RT et al. Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factor-dependent manner. J Biol Chem 2011; 286:13869-13878. https://doi.org/10.1074/jbc.M110.175414Chen R, Dioum EM, Hogg RT et al. Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factor-dependent manner. J Biol Chem 2011; 286:13869-13878. https://doi.org/10.1074/jbc.M110.175414Usrds I. Annual Data Report: Atlas of End-Stage-Renal-Disease in the United States. 2011Usrds I. Annual Data Report: Atlas of End-Stage-Renal-Disease in the United States. 2011Kitada M, Takeda A, Nagai T et al. Dietary restriction ameliorates diabetic nephropathy through anti-inflammatory effects and regulation of the autophagy via restoration of Sirt1 in diabetic Wistar fatty (fa/fa) rats: a model of type 2 diabetes. Exp Diabetes Res 2011b; 2011:908185. https://doi.org/10.1155/2011/908185Kitada M, Takeda A, Nagai T et al. Dietary restriction ameliorates diabetic nephropathy through anti-inflammatory effects and regulation of the autophagy via restoration of Sirt1 in diabetic Wistar fatty (fa/fa) rats: a model of type 2 diabetes. Exp Diabetes Res 2011b; 2011:908185. https://doi.org/10.1155/2011/908185Kitada M, Kume S, Imaizumi N, Koya D. Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of MnSOD dysfunction in AMPK/SIRT1-independent pathway. Diabetes 2011a; 60:634-643. https://doi.org/10.2337/db10-0386Kitada M, Kume S, Imaizumi N, Koya D. Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of MnSOD dysfunction in AMPK/SIRT1-independent pathway. Diabetes 2011a; 60:634-643. https://doi.org/10.2337/db10-0386Kim MY, Lim JH, Youn HH et al. Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1alpha axis in db/db mice. Diabetologia 2013; 56:204-217. https://doi.org/10.1007/s00125-012-2747-2Kim MY, Lim JH, Youn HH et al. Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1alpha axis in db/db mice. Diabetologia 2013; 56:204-217. https://doi.org/10.1007/s00125-012-2747-2Hasegawa K, Wakino S, Simic P et al. Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes. Nat Med 2013; 19:14961504. https://doi.org/10.1038/nm.3363Hasegawa K, Wakino S, Simic P et al. Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes. Nat Med 2013; 19:14961504. https://doi.org/10.1038/nm.3363Liu R, Zhong X Li X et al. Role of transcription factor acetylation in diabetic kidney disease. Diabetes 2014; 63:2440-2453. https://doi.org/10.2337/db13-1810Liu R, Zhong X Li X et al. Role of transcription factor acetylation in diabetic kidney disease. Diabetes 2014; 63:2440-2453. https://doi.org/10.2337/db13-1810Chuang PX Xu J, Dai Y et al. In vivo RNA interference models of inducible and reversible Sirt1 knockdown in kidney cells. Am J Pathol 2014;184:1940-1956. https://doi.org/10.1016/j.ajpath.2014.03.016Chuang PX Xu J, Dai Y et al. In vivo RNA interference models of inducible and reversible Sirt1 knockdown in kidney cells. Am J Pathol 2014;184:1940-1956. https://doi.org/10.1016/j.ajpath.2014.03.016Lo CS, Shi Y Chenier I et al. Heterogeneous nuclear ribo-nucleoprotein f stimulates sirtuin-1 gene expression and attenuates nephropathy progression in diabetic mice. Diabetes 2017; 66:1964-1978. https://doi.org/10.2337/db16-1588Lo CS, Shi Y Chenier I et al. Heterogeneous nuclear ribo-nucleoprotein f stimulates sirtuin-1 gene expression and attenuates nephropathy progression in diabetic mice. Diabetes 2017; 66:1964-1978. https://doi.org/10.2337/db16-1588Hou S, Zhang T, Li Y et al. Glycyrrhizic acid prevents diabetic nephropathy by activating AMPK/SIRT1/PGC-1alpha signaling in db/db mice. J Diabetes Res 2017; 2017:2865912. https://doi.org/10.1155/2017/2865912Hou S, Zhang T, Li Y et al. Glycyrrhizic acid prevents diabetic nephropathy by activating AMPK/SIRT1/PGC-1alpha signaling in db/db mice. J Diabetes Res 2017; 2017:2865912. https://doi.org/10.1155/2017/2865912Li X, Cai W, Lee K et al. Puerarin attenuates diabetic kidney injury through the suppression of NOX4 expression in podocytes. Sci Rep 2017; 7:14603. https://doi.org/10.1038/s41598-017-17925-7Li X, Cai W, Lee K et al. Puerarin attenuates diabetic kidney injury through the suppression of NOX4 expression in podocytes. Sci Rep 2017; 7:14603. https://doi.org/10.1038/s41598-017-17925-7Du YG, Zhang KN, Gao ZL et al. Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-kappaB pathway. Exp TherMed2018; 15:2156-2164. https://doi.org/10.3892/etm.2017.5621Du YG, Zhang KN, Gao ZL et al. Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-kappaB pathway. Exp TherMed2018; 15:2156-2164. https://doi.org/10.3892/etm.2017.5621Hong Q, Zhang L, Das B et al. Increased podocyte Sir-tuin1 function attenuates diabetic kidney injury. Kidney Int 2018; 93:1330-1343. https://doi.org/10.1016Zj.kint.2017.12.008Hong Q, Zhang L, Das B et al. Increased podocyte Sir-tuin1 function attenuates diabetic kidney injury. Kidney Int 2018; 93:1330-1343. https://doi.org/10.1016Zj.kint.2017.12.008Maeda S, Koya D, Araki SI et al. Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes. Clin Exp Nephrol 2011; 15:381-390. https://doi.org/10.1007/s10157-011-0418-0Maeda S, Koya D, Araki SI et al. Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes. Clin Exp Nephrol 2011; 15:381-390. https://doi.org/10.1007/s10157-011-0418-0Kume S, Thomas MC, Koya D. Nutrient sensing, autophagy, and diabetic nephropathy. Diabetes 2012; 61:23-29. https://doi.org/10.2337/db11-0555Kume S, Thomas MC, Koya D. Nutrient sensing, autophagy, and diabetic nephropathy. Diabetes 2012; 61:23-29. https://doi.org/10.2337/db11-0555Kitada M, OguraX Monno I, Koya D. Regulating autophagy as a therapeutic target for diabetic nephropathy. Curr Diab Rep 2017; 17:53. https://doi.org/10.1007/s11892-017-0879-yKitada M, OguraX Monno I, Koya D. Regulating autophagy as a therapeutic target for diabetic nephropathy. Curr Diab Rep 2017; 17:53. https://doi.org/10.1007/s11892-017-0879-yWen D, Huang X, Zhang M et al. Resveratrol attenuates diabetic nephropathy via modulating angiogenesis. PLoS ONE 2013; 8:e82336. https://doi.org/10.1371/journal.pone.0082336Wen D, Huang X, Zhang M et al. Resveratrol attenuates diabetic nephropathy via modulating angiogenesis. PLoS ONE 2013; 8:e82336. https://doi.org/10.1371/journal.pone.0082336Fan H, Yang HC, You L et al. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/ reperfusion-induced acute kidney injury. Kidney Int 2013; 83:404413. https://doi.org/10.1038/ki.2012.394Fan H, Yang HC, You L et al. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/ reperfusion-induced acute kidney injury. Kidney Int 2013; 83:404413. https://doi.org/10.1038/ki.2012.394Nakatani X Inagi R. Epigenetic regulation through SIRT1 in podocytes. Curr Hypertens Rev 2016; 12:89-94. https://doi.org/10.2174/1573402112666160302102515Nakatani X Inagi R. Epigenetic regulation through SIRT1 in podocytes. Curr Hypertens Rev 2016; 12:89-94. https://doi.org/10.2174/1573402112666160302102515Hao CM, Haase VH. Sirtuins and their relevance to the kidney. J Am Soc Nephrol 2010; 21:1620-1627. https://doi.org/10.1681/ASN.2010010046Hao CM, Haase VH. Sirtuins and their relevance to the kidney. J Am Soc Nephrol 2010; 21:1620-1627. https://doi.org/10.1681/ASN.2010010046Morigi M, Perico L, Benigni A. Sirtuins in renal health and disease. J Am Soc Nephrol 2018; 29:1799-1809. https://doi.org/10.1681/ASN.2017111218Morigi M, Perico L, Benigni A. Sirtuins in renal health and disease. J Am Soc Nephrol 2018; 29:1799-1809. https://doi.org/10.1681/ASN.2017111218Berthier CC, Zhang H, Schin M et al. Enhanced expression of Janus kinase-signal transducer and activator of transcription pathway members in human diabetic nephropathy. Diabetes 2009; 58:469-477. https://doi.org/10.2337/db08-1328Berthier CC, Zhang H, Schin M et al. Enhanced expression of Janus kinase-signal transducer and activator of transcription pathway members in human diabetic nephropathy. Diabetes 2009; 58:469-477. https://doi.org/10.2337/db08-1328Schmid H, Boucherot A, Yasuda Y et al. Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy. Diabetes 2006; 55:2993-3003. https://doi.org/10.2337/db06-0477Schmid H, Boucherot A, Yasuda Y et al. Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy. Diabetes 2006; 55:2993-3003. https://doi.org/10.2337/db06-0477Niranjan T, Bielesz B, Gruenwald A et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med 2008; 14:290-298. https://doi.org/10.1038/nm1731Niranjan T, Bielesz B, Gruenwald A et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med 2008; 14:290-298. https://doi.org/10.1038/nm1731Tikoo K, Tripathi DN, Kabra DG et al. Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53. FEBS Lett 2007; 581:1071-1078. https://doi.org/10.1016/j.febslet.2007.02.006Tikoo K, Tripathi DN, Kabra DG et al. Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53. FEBS Lett 2007; 581:1071-1078. https://doi.org/10.1016/j.febslet.2007.02.006Brezniceanu ML, Liu F, Wei CC et al. Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice. Kidney Int 2007; 71:912-923. https://doi.org/10.1038/sj.ki.5002188Brezniceanu ML, Liu F, Wei CC et al. Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice. Kidney Int 2007; 71:912-923. https://doi.org/10.1038/sj.ki.5002188Tran D, Bergholz J, Zhang H et al. Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence. Aging Cell2014; 13:669-678. https://doi.org/10.1111/acel.12219Tran D, Bergholz J, Zhang H et al. Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence. Aging Cell2014; 13:669-678. https://doi.org/10.1111/acel.12219Xiong S, Salazar G, Patrushev N et al. Peroxisome proliferator-activated receptor gamma coactivator1alpha is a central negative regulator of vascular senescence. Arterioscler Thromb Vasc Biol 2013; 33:988-998. https://doi.org/10.1161/ATVBAHA.112.301019Xiong S, Salazar G, Patrushev N et al. Peroxisome proliferator-activated receptor gamma coactivator1alpha is a central negative regulator of vascular senescence. Arterioscler Thromb Vasc Biol 2013; 33:988-998. https://doi.org/10.1161/ATVBAHA.112.301019Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol 2014; 24:464-471. https://doi.org/10.1016/j.tcb.2014.04.002Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol 2014; 24:464-471. https://doi.org/10.1016/j.tcb.2014.04.002Yuan X Huang S, Wang W et al. Activation of peroxisome proliferator-activated receptor-gamma coactivator 1alpha ameliorates mitochondrial dysfunction and protects podocytes from aldosterone-induced injury. Kidney Int 2012; 82:771-789. https://doi.org/10.1038/ki.2012.188Yuan X Huang S, Wang W et al. Activation of peroxisome proliferator-activated receptor-gamma coactivator 1alpha ameliorates mitochondrial dysfunction and protects podocytes from aldosterone-induced injury. Kidney Int 2012; 82:771-789. https://doi.org/10.1038/ki.2012.188Lv J, Jiang S, Yang Z et al. PGC-1alpha sparks the fire of neuroprotection against neurodegenerative disorders. Ageing Res Rev 2018; 44:8-21. https://doi.org/10.1016/j.arr.2018.03.004Lv J, Jiang S, Yang Z et al. PGC-1alpha sparks the fire of neuroprotection against neurodegenerative disorders. Ageing Res Rev 2018; 44:8-21. https://doi.org/10.1016/j.arr.2018.03.004Chen J, Xavier S, Moskowitz-Kassai E et al. Cathepsin cleavage of sirtuin 1 in endothelial progenitor cells mediates stress-induced premature senescence. Am J Pathol 2012; 180:973-983. https://doi.org/10.1016/j.ajpath.2011.11.033Chen J, Xavier S, Moskowitz-Kassai E et al. Cathepsin cleavage of sirtuin 1 in endothelial progenitor cells mediates stress-induced premature senescence. Am J Pathol 2012; 180:973-983. https://doi.org/10.1016/j.ajpath.2011.11.033Portilla D. Apoptosis, fibrosis and senescence. Nephron Clin Pract 2014; 127:65-69. https://doi.org/10.1159/000363717Portilla D. Apoptosis, fibrosis and senescence. Nephron Clin Pract 2014; 127:65-69. https://doi.org/10.1159/000363717Clements ME, Chaber CJ, Ledbetter SR, Zuk A. Increased cellular senescence and vascular rarefaction exacerbate the progression of kidney fibrosis in aged mice following transient ischemic injury. PLoS ONE2013; 8:e70464. https://doi.org/10.1371/journal.pone.0070464Clements ME, Chaber CJ, Ledbetter SR, Zuk A. Increased cellular senescence and vascular rarefaction exacerbate the progression of kidney fibrosis in aged mice following transient ischemic injury. PLoS ONE2013; 8:e70464. https://doi.org/10.1371/journal.pone.0070464Chuang PX Cai W, Li X et al. Reduction in podocyte SIRT1 accelerates kidney injury in aging mice. Am J Physiol Renal Physiol 2017; 313:F621-628. https://doi.org/10.1152/ajpre-nal.00255.2017Chuang PX Cai W, Li X et al. Reduction in podocyte SIRT1 accelerates kidney injury in aging mice. Am J Physiol Renal Physiol 2017; 313:F621-628. https://doi.org/10.1152/ajpre-nal.00255.2017Li J, Qu X, Ricardo SD, Bertram JF, Nikolic-Paterson DJ. Resveratrol inhibits renal fibrosis in the obstructed kidney: potential role in deacetylation of Smad3. Am J Pathol 2010; 177:1065-1071. https://doi.org/10.2353/ajpath.2010.090923Li J, Qu X, Ricardo SD, Bertram JF, Nikolic-Paterson DJ. Resveratrol inhibits renal fibrosis in the obstructed kidney: potential role in deacetylation of Smad3. Am J Pathol 2010; 177:1065-1071. https://doi.org/10.2353/ajpath.2010.090923Huang KP, Chen C, Hao J et al. AGEs-RAGE system down-regulates Sirt1 through the ubiquitin-proteasome pathway to promote FN and TGF-beta1 expression in male rat glomerular mesangial cells. Endocrinology 2015; 156:268-279. https://doi.org/10.1210/en.2014-1381Huang KP, Chen C, Hao J et al. AGEs-RAGE system down-regulates Sirt1 through the ubiquitin-proteasome pathway to promote FN and TGF-beta1 expression in male rat glomerular mesangial cells. Endocrinology 2015; 156:268-279. https://doi.org/10.1210/en.2014-1381Beher D, Wu J, Cumine S et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des 2009; 74:619-624. https://doi.org/10.1111/j.1747-0285.2009.00901.xBeher D, Wu J, Cumine S et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des 2009; 74:619-624. https://doi.org/10.1111/j.1747-0285.2009.00901.xPacholec M, Bleasdale JE, Chrunyk B et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 2010; 285:8340-8351. https://doi.org/10.1074/jbc.M109.088682Pacholec M, Bleasdale JE, Chrunyk B et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 2010; 285:8340-8351. https://doi.org/10.1074/jbc.M109.088682Rogacka D, Audzeyenka I, Rychlowski M et al. Metformin overcomes high glucose-induced insulin resistance of podocytes by pleiotropic effects on SIRT1 and AMPK. Biochim Biophys Acta 2018; 1864:115-125. https://doi.org/10.1016/j.bbadis.2017.10.014Rogacka D, Audzeyenka I, Rychlowski M et al. Metformin overcomes high glucose-induced insulin resistance of podocytes by pleiotropic effects on SIRT1 and AMPK. Biochim Biophys Acta 2018; 1864:115-125. https://doi.org/10.1016/j.bbadis.2017.10.014Sanchez R, Meslamani J, Zhou MM. The bromodo-main: from epigenome reader to druggable target. Biochim Biophys Acta 2014; 1839:676-685. https://doi.org/10.1016/j.bbagrm.2014.03.011Sanchez R, Meslamani J, Zhou MM. The bromodo-main: from epigenome reader to druggable target. Biochim Biophys Acta 2014; 1839:676-685. https://doi.org/10.1016/j.bbagrm.2014.03.011Huang B, Yang XD, Zhou MM et al. Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA. Mol Cell Biol 2009;29:1375-1387. https://doi.org/10.1128/MCB.01365-08Huang B, Yang XD, Zhou MM et al. Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA. Mol Cell Biol 2009;29:1375-1387. https://doi.org/10.1128/MCB.01365-08

The authors declare that there are no conflicts of interest present.