Cordyceps sinensis ameliorates renal interstitial fibrosis in mice by IL-6 trans-signaling pathway
10.3969/j.issn.1672-8467.2025.01.001
- VernacularTitle:冬虫夏草通过IL-6反式信号通路改善小鼠肾间质纤维化
- Author:
Ying-xue SUN
1
;
Jun CHEN
;
Pei-chen TANG
;
Jian ZHANG
;
Wei-ze CHEN
;
Zhi-xin YAN
;
Na-na SONG
Author Information
1. 复旦大学附属中山医院肾内科 上海 200032
- Publication Type:Journal Article
- Keywords:
cordyceps sinensis(CS);
chronic kidney disease(CKD);
fibroblast;
IL-6 trans-signaling pathway;
renal fibrosis;
mouse
- From:
Fudan University Journal of Medical Sciences
2025;52(1):1-15
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of cordyceps sinensis(CS)on the activation of fibroblasts through IL-6 trans-signaling pathway and its specific mechanism in the treatment of renal fibrosis.Methods Renal fibrosis mouse model was established by unilateral ischemia/reperfusion(UIR),and the mice were administered intragastrically CS,soluble glycoprotein 130 Fc(sgp130Fc)or Hyper-IL-6.Masson's trichrome staining was utilized to identify tubulointerstitial fibrosis.PAS staining was utilized to assess the extent of renal injury.Western blot was employed to analyze the expression levels of fibrosis markers[alpha-smooth muscle actin(α-SMA),fibronectin(FN)]and proteins associated with IL-6 trans-signaling pathway[phosphorylated signal transducer and activator of transcription 3(p-STAT3),soluble interleukin-6 receptor(sIL-6R)].The expression and localization of proteins were additionally detected by immunohistochemistry,immunofluorescence and qPCR.The effect of cordyceps sinensis extract cordycepin on IL-6 trans-signaling in fibroblasts was further investigated in vitro.Results The results from in vivo experiments showed that administration of CS during the chronic phase demonstrated a beneficial protective impact on inflammation and fibrosis in the affected kidney,and serum creatinine levels and collagen deposition were decreased.Western blot analysis revealed a decrease in the expression levels of α-SMA,FN,as well as IL-6 trans-signaling pathway protein p-STAT3,sIL-6R in the treatment group.Additionally,the mRNA expression levels of chemokines monocyte chemoattractant protein-1(MCP-1)and C-X-C motif chemokine ligand 12(CXCL12)were also decreased in the CS treatment group.Additionally,Hyper-IL-6 can partially counteract the therapeutic effects of CS.In vitro experiments further demonstrated that cordycepin inhibited the secretion of IL-6 from NRK-52E.Combined treatment of recombinant IL-6 and sIL-6R protein activated NRK-49F,leading to a significant increase in α-SMA,FN,and p-STAT3 expression levels.Cordycepin or sgp130Fc treatment significantly inhibited the proliferation of fibroblasts induced by IL-6 trans-signaling pathway.Conclusion CS can significantly reduce IL-6 secretion by renal tubular epithelial cells and inhibit the activation of IL-6 trans-signaling pathway in fibroblasts,thereby ameliorating renal interstitial fibrosis.
