Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/34606
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    Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/34606


    Title: The Histone Demethylase Inhibitor GSK-J4 Is a Therapeutic Target for the Kidney Fibrosis of Diabetic Kidney Disease via DKK1 Modulation
    Authors: Hung, Peir-Haur
    Hsu, Yung-Chien
    Chen, Tsung-Hsien
    Ho, Cheng
    Lin, Chun-Liang
    Contributors: Department of Applied Life Science and Health, Chia Nan University of Pharmacy & Science
    Chang Gung Memorial Hospital
    Keywords: growth-factor-beta
    hyperglycemia
    phosphorylation
    inflammation
    mechanisms
    dickkopf-1
    matrix
    cells
    jnk
    emt
    Date: 2022
    Issue Date: 2023-12-11 14:00:26 (UTC+8)
    Publisher: MDPI
    Abstract: 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.
    Relation: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, n.16, 9407
    Appears in Collections:[Dept. of Life and Health Science] Periodical Articles

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