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Yiqi Tongluo Formula alleviates renal fibrosis in UUO rats via the miR-21a-3p/TGF-β1/Smad3 axis
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DOI   10.11656/j.issn.1672-1519.2026.04.15
Key Words   renal interstitial fibrosis;unilateral ureteral obstruction;Yiqi Tongluo Formula;miR-21a-3p/TGF-β1/Smad3 axis
Author NameAffiliationE-mail
ZHANG Wenlei Suzhou Wujiang District Hospital of Traditional Chinese Medicine, Suzhou 215200, China  
YU Kena Nanjing University of Chinese Medicine, Nanjing 210029, China  
YIN Xiaofan Nanjing University of Chinese Medicine, Nanjing 210029, China  
SONG Qin Nanjing University of Chinese Medicine, Nanjing 210029, China  
YANG Jialing Suzhou Wujiang District Hospital of Traditional Chinese Medicine, Suzhou 215200, China  
ZHAO Jing Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210029, China  
SUN Wei Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210029, China  
WANG Yaoguang First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China wangyaoguang1012@126.com 
HE Weiming Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210029, China yfy0019@njucm.edu.cn 
Abstract
    [Objective] This study investigates the effect of miR-21a-3p on transforming growth factor-β1(TGF-β1)-induced renal tubular epithelial cell(NRK-52E) fibrosis and unilateral ureteral obstruction(UUO) rat models,and explores the mechanism of Yiqi Tongluo Formula in anti-renal fibrosis via the miR-21a-3p/TGF-β1/Smad3 axis. [Methods] The miR-21a-3p was first identified as significantly upregulated in renal fibrosis rat models through the Gene Expression Omnibus(GEO) database. A TGF-β1-induced NRK-52E fibrosis model was established for validation. Cell experiments included normal control,disease model,inhibitor negative control,and miR-21a-3p inhibitor groups. RT-qPCR measured miR-21a-3p expression,while Western blot detected fibrosis markers(collagen I,fibronectin) and epithelial-mesenchymal transition(EMT) markers(α-SMA,E-cadherin). Animal experiments divided rats into six groups:sham-operated,model,low/medium/high-dose Yiqi Tongluo Formula,and losartan potassium groups(n=10 per group). UUO model rats received interventions for two weeks. HE and Masson staining evaluated renal pathology,RT-qPCR measured miR-21a-3p,collagen I,fibronectin,and TGF-β1 mRNA levels,and Western blot assessed TGF-β1,Smad3,p-Smad3,α-SMA,and E-cadherin protein expression. [Results] In cells,the model and inhibitor negative control groups showed significantly upregulated miR-21a-3p,collagen I,fibronectin,and α-SMA with downregulated E-cadherin compared to normal controls. The miR-21a-3p inhibitor group reversed these changes. In UUO rats,the model group exhibited severe fibrosis,increased collagen volume,and elevated miR-21a-3p,collagen I,fibronectin,and TGF-β1 expression versus sham group. Yiqi Tongluo Formula and losartan potassium alleviated fibrosis,reduced collagen volume,and downregulated miR-21a-3p,TGF-β1,p-Smad3/Smad3,and α-SMA while upregulating E-cadherin. [Conclusion] Yiqi Tongluo Formula may inhibit renal fibrosis by suppressing miR-21a-3p expression,blocking TGF-β1/Smad3 signaling,and reducing extracellular matrix production and EMT.

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