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| 標題: | The Histone Demethylase Inhibitor GSK-J4 Is a Therapeutic Target for the Kidney Fibrosis of Diabetic Kidney Disease via DKK1 Modulation |
| 作者: | Hung, Peir-Haur
Hsu, Yung-Chien
Chen, Tsung-Hsien
Ho, Cheng
Lin, Chun-Liang |
| 貢獻者: | Department of Applied Life Science and Health, Chia Nan University of Pharmacy & Science
Chang Gung Memorial Hospital |
| 關鍵字: | growth-factor-beta
hyperglycemia
phosphorylation
inflammation
mechanisms
dickkopf-1
matrix
cells
jnk
emt |
| 日期: | 2022 |
| 上傳時間: | 2023-12-11 14:00:26 (UTC+8) |
| 出版者: | MDPI |
| 摘要: | Diabetic kidney disease (DKD) can cause inflammation and fibrosis, in addition to being the main complication of diabetes. Among many factors, epigenetic alterations in aberrant histone modifications play a key role in causing DKD. In this study, the mechanism of GSK-J4, a histone demethylase KDM6A inhibitor, was evaluated in streptozotocin-induced diabetic mice. It was confirmed that GSK-J4, via dickkopf-1 (DKK1) modulation, could significantly reduce proteinuria and glomerulosclerosis in diabetic mice. The mRNA accumulation levels of DKK1, TGF-beta 1, fibronectin, and collagen IV were significantly elevated in diabetic mice. In contrast, the mRNA accumulations of those genes were significantly reduced in diabetic mice treated with GSK-J4 compared to those in diabetic mice, relatively speaking. The protein accumulation levels of fibronectin and collagen IV were significantly elevated in diabetic mice. Furthermore, GSK-J4 attenuated the high glucose-induced expression of profibrotic factors in mesangial cells via DKK1. In conclusion, our study provides a novel strategy to eliminate fibrosis in the kidneys of DKD mice. Using GSK-J4 reduces DKK1 expression, thereby ameliorating renal insufficiency, glomerulosclerosis morphological abnormalities, inflammation, and fibrosis in diabetic mice. |
| 關聯: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, n.16, 9407 |
| 顯示於類別: | [生活保健科技系] 期刊論文
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