資料載入中.....
|
請使用永久網址來引用或連結此文件:
https://ir.cnu.edu.tw/handle/310902800/34606
|
| 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: | Chia Nan University of Pharmacy & Science
Chang Gung Memorial Hospital
Chang Gung Memorial Hospital
Chang Gung Memorial Hospital
Chang Gung Memorial Hospital
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.CB2, pp.CC2, pp.-, |
| 顯示於類別: | [行政單位] 123
|
文件中的檔案:
| 檔案 |
描述 |
大小 | 格式 | 瀏覽次數 |
|---|
| index.html | | 0Kb | HTML | 84 | 檢視/開啟 |
|
在CNU IR中所有的資料項目都受到原著作權保護.
|
