Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis
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...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2017/7242384 |
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| _version_ | 1832554544830087168 |
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| author | Jing Sun Yangwei Wang Wenpeng Cui Yan Lou Guangdong Sun Dongmei Zhang Lining Miao |
| author_facet | Jing Sun Yangwei Wang Wenpeng Cui Yan Lou Guangdong Sun Dongmei Zhang Lining Miao |
| author_sort | Jing Sun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1073091b18bd47c19a3ffcb238b7a262 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-1073091b18bd47c19a3ffcb238b7a2622025-02-03T05:51:05ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/72423847242384Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal FibrosisJing Sun0Yangwei Wang1Wenpeng Cui2Yan Lou3Guangdong Sun4Dongmei Zhang5Lining Miao6Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, ChinaDepartment of Nephrology, Second Hospital of Jilin University, Changchun 130041, ChinaDepartment of Nephrology, Second Hospital of Jilin University, Changchun 130041, ChinaDepartment of Nephrology, Second Hospital of Jilin University, Changchun 130041, ChinaDepartment of Nephrology, Second Hospital of Jilin University, Changchun 130041, ChinaDepartment of Nephrology, Second Hospital of Jilin University, Changchun 130041, ChinaDepartment of Nephrology, Second Hospital of Jilin University, Changchun 130041, ChinaOne 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.http://dx.doi.org/10.1155/2017/7242384 |
| spellingShingle | Jing Sun Yangwei Wang Wenpeng Cui Yan Lou Guangdong Sun Dongmei Zhang Lining Miao Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis Journal of Diabetes Research |
| title | Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis |
| title_full | Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis |
| title_fullStr | Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis |
| title_full_unstemmed | Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis |
| title_short | Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis |
| title_sort | role of epigenetic histone modifications in diabetic kidney disease involving renal fibrosis |
| url | http://dx.doi.org/10.1155/2017/7242384 |
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