Abstract
One of the commonest causes of end-stage renal disease is diabetic kidney disease (DKD). Renal fibrosis, characterized by the accumulation of extracellular matrix (ECM) proteins in glomerular basement membranes and the tubulointerstitium, is the final manifestation of DKD. The TGF-β pathway triggers epithelial-to-mesenchymal transition (EMT), which plays a key role in the accumulation of ECM proteins in DKD. DCCT/EDIC studies have shown that DKD often persists and progresses despite glycemic control in diabetes once DKD sets in due to prior exposure to hyperglycemia called “metabolic memory.” These imply that epigenetic factors modulate kidney gene expression. There is evidence to suggest that in diabetes and hyperglycemia, epigenetic histone modifications have a significant effect in modulating renal fibrotic and ECM gene expression induced by TGF-β1, as well as its downstream profibrotic genes. Histone modifications are also implicated in renal fibrosis through its ability to regulate the EMT process triggered by TGF-β signaling. In view of this, efforts are being made to develop HAT, HDAC, and HMT inhibitors to delay, stop, or even reverse DKD. In this review, we outline the latest advances that are being made to regulate histone modifications involved in DKD.
Highlights
One of the main causes of end-stage renal disease is diabetic kidney disease (DKD) [1]
In both in vitro and in vivo investigations related to diabetes, it has been demonstrated that histone lysine methylation and acetylation patterns changed, along with the recruitment of histone acetyltransferases (HATs)/histone deacetylases (HDACs) or histone methyltransferases (HMTs) at gene promoters [6, 48, 56, 57]
It has been widely believed that epithelial-to-mesenchymal transition (EMT) is triggered by transforming growth factor-β1 (TGF-β1), which is an outstanding mechanism in the progression of fibrosis due to DKD [66], and this can be countered and reversed by BMP-7 [34]
Summary
One of the main causes of end-stage renal disease is diabetic kidney disease (DKD) [1]. The exact cause of DKD is unknown, several factors including genetic, environmental, and hemodynamic factors; high blood glucose; high blood lipids; hypertension; and proteinuria contribute to its development [2] All these factors appear to modulate the production and action of various growth factors/ cytokines and reactive oxygen species (ROS), which will give rise to podocyte damage and interstitial inflammation that participate in the pathogenesis of DKD. This complex set of events leads to glomerular dysfunction and renal failure due to the deposition of excess extracellular matrix (ECM) proteins and increase in renal glomerulosclerosis [2, 3]. These evidences suggest that epigenetics may have a significant role in the pathobiology of DKD [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
