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General Physiology and Biophysics Vol.40, No.2, p.147–154, 2021 |
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Title: microRNA let-7i-5p aggravates kidney fibrosis via targeting GALNT1 | ||
Author: Chen-Min Sun, Wen-Yi Zhang, Shu-Yan Wang, Gang Qian, Dong-Liang Pei, Guang-Ming Zhang | ||
Abstract: Renal fibrosis poses critical health problem. We aimed to investigate role of let-7i-5p in renal fibrosis. In silico reproduction of Mouse Kidney FibrOmics browser was used to identify potential target of let-7i-5p. In vivo validation was conducted in C57BL/6 mice with unilateral ureteral obstruction (UUO) and folic acid (FA) induction. In vitro validation was performed in transforming growth factor (TGF)-β1-treated HK-2 cells. Mimics and inhibitors of let-7i-5p, and target gene polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1) were monitored by RT-PCR and Western blotting. Fibrosis markers, injury markers, and house-keeping genes were evaluated. Levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in serum and media were measured by ELISA. In silico analysis showed gradual increase of let-7i-5p and decrease of GALNT1 over time and the combination was validated both in mouse and human miR-gene target prediction databases. Expression of GALNT1 decreased while expression of let-7i-5p increased in renal tissues of both UUO and FA mice. Serum IL-6, IL-1β, and TNF-α levels were elevated in vivo. In vitro models revealed negative correlation between expression levels of let-7i-5p and GALNT1. Overexpression of let-7i-5p inhibited GALNT1 expression and reduced release of inflammatory factors. In conclusion, overexpression of GALNT1 may combat the inflammation induced by let-7i-5p. |
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Keywords: Renal fibrosis — GALNT1 — let-7i-5p — Inflammation | ||
Published online: 07-Apr-2021 | ||
Year: 2021, Volume: 40, Issue: 2 | Page From: 147, Page To: 154 | |
doi:10.4149/gpb_20210031 |
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