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Mechanism of action of Jinchan Yishen Tongluo Formula in inhibiting epithelial mesenchymal transition of epithelial cells in mice with diabetic kidney disease through KLF4/SMAD pathway
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DOI   10.11656/j.issn.1672-1519.2026.01.16
Key Words   diabetic kidney disease;epithelial mesenchymal transition;Jinchan Yishen Tongluo Formula;KLF4/SMAD pathway
Author NameAffiliationE-mail
ZHANG Kexin Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing 100040, China  
HE Peiyue Key Laboratory of Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing 100007, China  
TANG Jingyi Key Laboratory of Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing 100007, China  
ZHANG Zeyu Key Laboratory of Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing 100007, China  
GUO Xi Key Laboratory of Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing 100007, China  
WU Yuqi Key Laboratory of Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing 100007, China  
LIU Yuning Key Laboratory of Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing 100007, China  
JI Yue Key Laboratory of Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing 100007, China drji_yue@163.com 
Abstract
    [Objective] Diabetic kidney disease(DKD)is an important microvascular complication of diabetes mellitus. The clinical effect of Jinchan Yishen Tongluo Formula(JCYSTL) in the treatment of diabetic kidney disease is significant,but its specific mechanism of action remains to be further explored. [Methods] In this experiment,we took the DKD model of C57BL/6J mice induced by high-fat diet combined with streptozotocin as the research object and used JCYSTL for intervention. The therapeutic effect of JCYSTL on DKD mice was evaluated by detecting 24-hour urinary protein(24 h-UPQ),serum creatinine(Scr),blood urea nitrogen (BUN),hematoxylineosin staining(HE)and Masson staining. The expression levels of epithelial-mesenchymal transition markers [zonula occludens-1(ZO-1),E-cadherin(E-cad),vimentin(VIM),α-smooth muscle actin(α-SMA)] were detected by Western blot to clarify the effect of JCYSTL on epithelial-mesenchymal transition in renal tissue of DKD mice. The expressions of Kruppel-like factor 4 (KLF4),Sma and Mad-related protein 7(SMAD7)and Sma and Mad-related protein 3(SMAD3)were detected by RT-qPCR and Western blot to observe the effect of JCYSTL on the expression levels of main proteins in the KLF4/SMAD pathway. [Results] Our results showed that JCYSTL significantly reduced the levels of blood glucose,24 h-UPQ,Scr and BUN in DKD mice,and improved glomerular basement membrane thickening and collagen deposition. Western blot showed that JCYSTL up-regulated the expressions of ZO-1 and E-cad,inhibited VIM and α-SMA,promoted the expressions of KLF4 and SMAD7,and inhibited the expression of SMAD3. [Conclusion] Therefore,we believe that JCYSTL may alleviate DKD by activating the KLF4/SMAD pathway to inhibit EMT.

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