Shenxiankang attenuates renal fibrosis in UUO mice via DANCR/TGF-β1/Smad3 signaling axis
10.3969/j.issn.1000-4718.2025.08.010
- VernacularTitle:肾纤康通过调控DANCR/TGF-β1/Smad3信号轴缓解UUO小鼠肾纤维化
- Author:
Yue HUANG
1
;
Xiaomei LIU
;
Jianchun LI
;
Qiong ZHANG
;
Li WANG
;
Qiong-dan HU
Author Information
1. 西南医科大学附属中医医院肾内科,四川 泸州 646000;西南医科大学,四川 泸州 646000
- Publication Type:Journal Article
- Keywords:
Shenxiankang;
chronic kidney disease;
renal fibrosis;
DANCR/TGF-β1/Smad3 signaling axis
- From:
Chinese Journal of Pathophysiology
2025;41(8):1541-1549
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the efficacy of Shenxiankang(SXK)in mitigating renal fibrosis in unilateral ureteral obstruction(UUO)mice,and elucidate its regulatory mechanism targeting the differentiation antagonizing non-protein coding RNA(DANCR)/TGF-β1/Smad3 signaling axis.METHODS:Mice were randomly assigned to:normal group(NC),model group(UUO),low,medium and high doses(1 500,3 000 and 4 500 mg·kg-1·d-1)of SXK group,and benazepril(10 mg·kg-1·d-1)group.Chronic kidney disease was modeled via unilateral ureteral ligation.Renal DAN-CR overexpression was induced using tail vein injection coupled with ultrasound microbubble technology.In vitro,human renal tubular epithelial cells(HK-2)were stimulated with TGF-β1;DANCR was either knocked down or overexpressed,followed by SXK intervention in both in vivo and in vitro models.Renal tissues were harvested for pathological assessment.DANCR expression and localization were analyzed using fluorescence in situ hybridization.Fibrosis deposition was evaluat-ed by immunohistochemistry(IHC).Western blot quantified the expression of fibrosis markers(α-SMA,FN)and key components of the TGF-β1/Smad3 signaling axis(p-Smad3,Smad3,TGF-β1).RESULTS:UUO mice exhibited signifi-cant renal tubular dilation.SXK intervention ameliorated renal lesions and reduced fibrosis.In UUO mice with DANCR overexpression,levels of renal fibrosis markers(α-SMA,FN)and TGF-β1/Smad3 signaling axis proteins(p-Smad3,Smad3,TGF-β1)were increased;these effects were reversed by SXK.In vitro,DANCR knockdown decreased the expres-sion of fibrotic proteins/mRNA and TGF-β1/Smad3 signaling axis components.SXK treatment effectively counteracted the fibrotic injury and TGF-β1/Smad3 signaling axis activation induced by DANCR overexpression.CONCLUSION:SXK ef-fectively mitigates renal fibrosis in UUO mice,potentially through regulation of the DANCR/TGF-β1/Smad3 signaling axis.
