Mechanism of Shenfukang capsule in ameliorating renal interstitial fibrosis by regulating cellular crosstalk via the STAT3/YAP pathway
- VernacularTitle:肾福康胶囊通过STAT3/YAP通路调控细胞串扰改善肾间质纤维化的机制
- Author:
Wei DU
1
;
Yufang YANG
2
;
Yanhong LIAO
1
;
Xiaoqin ZOU
3
;
Zhiwei LIANG
1
;
Xiangqian FENG
1
;
Xiaobin ZHONG
1
Author Information
1. School of Pharmacy，Guangxi Medical University，Nanning 530021，China
2. Dept. of Pharmacy，the First Affiliated Hospital of Guangxi Medical University，Nanning 530021，China
3. Dept. of Scientific Research，the First Affiliated Hospital of Guangxi Medical University，Nanning 530021，China
- Publication Type:Journal Article
- Keywords:
Shenfukang capsule;
renal interstitial fibrosis;
macrophage;
fibroblast;
cellular crosstalk;
STAT3/YAP pathway
- From:
China Pharmacy
2026;37(12):1547-1552
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the mechanism by which Shenfukang capsule （SFK） ameliorates renal interstitial fibrosis （RIF） by regulating macrophage-fibroblast crosstalk via the signal transducer and activator of transcription 3 （STAT3）/Yes-associated protein （YAP） pathway. METHODS RAW264.7 macrophages were induced to polarize with transforming growth factor-β 1 （TGF-β 1 ）. Subsequently， a non-contact co-culture system of macrophages with renal fibroblasts NRK-49F， as well as a non-contact co-culture system of macrophages with YAP-knockdown renal fibroblasts， were established. Cells were treated with low， medium， and high concentrations （4， 8， 16 μg/mL） of SFK， as well as a STAT3 inhibitor （STAT3-I，1.64 μg/mL） and losartan potassium tablets （positive control， 0.28 μg/mL）， for 48 h. After intervention， the protein and mRNA expression levels of CD86， CD163， and STAT3 in macrophages， as well as CD86， F4/80， and STAT3 mRNA， were detected. In co-cultured renal fibroblasts， the protein and mRNA expression levels of α -smooth muscle actin （ α -SMA）， Vimentin， collagen type Ⅰ （Col-Ⅰ）， matrix metalloproteinase-1 （MMP-1）， and YAP were detected. In co-cultured YAP-knockdown renal fibroblasts， the protein and mRNA expression levels of α -SMA， Vimentin， and MMP-1 were also detected. RESULTS Following TGF-β 1 induction， the protein expression levels of CD86， CD163， and STAT3， as well as the mRNA expression levels of CD86， F4/80， and STAT3 in macrophages were significantly increased （ P ＜0.05）. The conditioned medium from polarized macrophages activated renal fibroblasts， as evidenced by significantly increased protein and mRNA expression levels of α -SMA， Vimentin， Col-Ⅰ， and YAP， and significantly decreased protein and mRNA expression levels of MMP-1 in renal fibroblasts （ P ＜0.05）. Treatment with SFK and STAT3-I reversed the changes in the above indicators， with the medium concentration SFK group showing stronge r effects on some indicators than the low and high concentration groups. In the non-contact co-culture experiment of macrophages and YAP-knockdown renal fibroblasts， there were no statistically significant differences in the protein and mRNA expression of α-SMA， Vimentin， and MMP-1 among the groups. CONCLUSIONS SFK can inhibit macrophage-renal fibroblast crosstalk by blocking the STAT3/YAP pathway， thereby delaying the progression of RIF.
