Epigenetic regulation of renal fibrosis in diabetic nephropathy: focus on histone modifications


DOI: https://dx.doi.org/10.18565/nephrology.2018.2.68-76

K.A. Aitbaev, I.T. Murkamilov, Zh.A. Murkamilova, V.V. Fomin

1 Research Institute of Molecular Biology and Medicine under the National Center for Cardiology and Therapy of the Ministry of Health of the Kyrgyz Republic; Bishkek, Kyrgyzstan; 2 I.K. Akhunbaev Kyrgyz State Medical Academy; Bishkek, Kyrgyzstan; 3 Acad. Mirsaid Mirrakhimov National Center for Cardiology and Therapy under the Ministry of Health of the Kyrgyz Republic; Bishkek, Kyrgyzstan; 4 Center for Family Medicine № 7; Bishkek, Kyrgyzstan; 5 FSBEI HE "Sechenov First Moscow State Medical University"; Moscow, Russia
One of the most common causes of the development of the end-stage renal disease is diabetic nephropathy (DNP). Renal fibrosis, characterized by the accumulation of extracellular matrix (ECM) proteins in the glomerular basement membrane and tubulointerstitial tissues, is the terminal manifestation of DPN. The signaling pathway of TGF-β (Transforming growth factor beta) triggers an epithelial-mesenchymal transition (EMT), which plays a key role in the accumulation of ECM proteins in DPN. The studies show that DNP continues to progress despite the glycemic control. This phenomenon is called "metabolic memory" and means that epigenetic factors, in particular histone modifications, alter the TGF-β1-induced of renal fibrosis gene and ECM protein expression, and also participate in renal fibrosis due to capability to regulate the EMT process caused by TGF-β signaling. In this regard, researchers are currently making efforts to develop agents affecting the histone modifications, in order to delay, stop, or even reverse the development of DPN. This review presents the results of the most recent studies on the regulation of histone modifications involved in the pathogenesis of DPN.
Keywords: metabolic memory, extracellular matrix proteins, renal fibrosis, histone modifications, diabetic nephropathy
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About the Autors

Aitbaev K.A. – Doctor of Medical Sciences, Professor, Head of the Laboratory of Pathological Physiology of the Research Institute of Molecular Biology and Medicine under the NCCT of the Ministry of Health of the Kyrgyz Republic; Bishkek, Kyrgyzstan
Murkamilov I.T. – PhD in Medical Sciences, Nephrologist of the 1-st qualification category, Teaching Assistant at the Department of Faculty Therapy, I.K. Akhunbaev KSMA; Bishkek; Kyrgyzstan. E-mail: murkamilov.i@mail.ru
Fomin V.V. – Doctor of Medical Sciences, Professor, Head of the Department of Faculty Therapy № 1, FSAEI HE Sechenov First Moscow State Medical University of RMH; Moscow.
Murkamilova Zh.A. – Nephrologist at the Center for Family Medicine № 7; Bishkek, Kyrgyzstan


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