miR-122-5p Regulates Renal Fibrosis In Vivo
Shohei Kaneko1, Katsunori Yanai1, Hiroki Ishii1
1Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan.
Abstract:
The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction showed that miR-122-5p was the most downregulated (0.28-fold) miRNA in the kidneys of UUO mice. The injection of an miR-122-5p mimic promoted renal fibrosis and upregulated COL1A2 and FN1, whereas an miR-122-5p inhibitor suppressed renal fibrosis and downregulated COL1A2 and FN1. The expression levels of fibrosis-related mRNAs, which were predicted targets of miR-122-5p, were evaluated. The expression level of TGFBR2, a pro-fibrotic mRNA, was upregulated by the miR-122-5p mimic, and the expression level of FOXO3, an anti-fibrotic mRNA, was upregulated by the miR-122-5p inhibitor. The protein expressions of TGFBR2 and FOXO3 were confirmed by immunohistochemistry. Additionally, the expression levels of LC3, downstream anti-fibrotic mRNAs of FOXO3, were upregulated by the miR-122-5p inhibitor. These results suggest that miR-122-5p has critical roles in renal fibrosis.
Insights
MicroRNAs (miRNAs) impact kidney fibrosis. Downregulated miR-122-5p exacerbates renal fibrosis by upregulating pro-fibrotic genes, while its inhibition protects against kidney fibrosis.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- The role of exogenous microRNAs (miRNAs) in renal fibrosis remains largely unknown.
- Renal fibrosis is a significant pathological process contributing to chronic kidney disease progression.
Purpose of the Study:
- To investigate the effect of exogenous microRNAs on renal fibrosis.
- To elucidate the specific role of miR-122-5p in the pathogenesis of renal fibrosis.
Main Methods:
- A unilateral ureteral obstruction (UUO) mouse model was utilized to induce renal fibrosis.
- miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were performed.
- The effects of miR-122-5p mimic and inhibitor on fibrosis markers and target gene expression were assessed.
Main Results:
- miR-122-5p was significantly downregulated in the kidneys of UUO mice.
- Overexpression of miR-122-5p promoted renal fibrosis and upregulated collagen type I alpha 2 chain (COL1A2) and fibronectin 1 (FN1).
- Inhibition of miR-122-5p suppressed renal fibrosis and downregulated COL1A2 and FN1, while upregulating anti-fibrotic FOXO3 and its downstream target LC3.
Conclusions:
- miR-122-5p plays a critical role in regulating renal fibrosis.
- Modulating miR-122-5p levels offers a potential therapeutic strategy for kidney fibrosis.
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