湖北医药学院学报2025，Vol.44Issue(6)：703-707,封3,6.DOI:10.13819/j.issn.2096-708X.2025.06.009
肾小管上皮特异性敲除Tgfbr2抑制Smad3磷酸化减轻UUO小鼠肾纤维化
Tubule-specific Deletion of Tgfbr2 Suppresses Phosphorylation of Smad3 and Attenuates UUO-induced Renal Fi-brosis in Mice
HU Lin 1YAO Song-yuan2
作者信息
- 1. Department of Endocrinology,Ankang Central Hospital,the Sixth Clinical School of Hubei University of Medicine,Ankang,Shaanxi 725000
- 2. School of Basic Medical Sciences,Hubei Univer-sity of Medicine,Shiyan,Hubei 442000,China
- 折叠
摘要
Abstract
Objective To investigate the impact and mechanism of specific deletion of transforming growth factor-β receptor type Ⅱ(Tgfbr2)in tubular epithelial cells on unilateral ureteral obstruction(UUO)-induced renal fibrosis in mice.Meth-ods Tubular epithelial cell-specific Tgfbr2 knockout mice(Tgfbr2tecKO)were prepared and studied in a 2×2 factorial de-sign(genotype:Tgfbr2f/f vs.Tgfbr2tecKO;surgery:Sham vs.UUO),with an UUO model established and Sham as control.Immunofluorescence(IF)was used to assess TGFBR2,E-cadherin,and AQP1/AQP3.Sirius Red staining was performed to quantify collagen deposition.Fibronectin(FN)and α-smooth muscle actin(α-SMA)were detected by immunohisto-chemistry(IHC).The phosphorylation of Smad3(p-Smad3)was measured by Western blot.Results Compared with Tgf-br2f/f controls,Tgfbr2tecKO mice had a marked reduction in TGFBR2 signaling as indicated by IF with ROI-based mean fluo-rescence intensity(IF-ROI-MFI).Under UUO,Tgfbr2tecKO mice displayed reduced collagen deposition(Sirius Red)and downregulated FN and α-SMA,while the expressions of E-cadherin and AQP1/AQP3,as well as their membrane localiza-tion were preserved.Western blot further demonstrated that Tgfbr2 deficiency significantly suppressed the upregulation of p-Smad3 induced by UUO.Two-way ANOVA highlighted the main effects of genotype and a genotype×surgery interaction(P＜0.05).Conclusion Tubule-specific deletion of Tgfbr2 inhibits the activation of Smad3,attenuates UUO-induced renal fibrosis,and preserves tubular epithelial structure and molecular phenotype,which provides experimental support for recep-tor-targeted,cell-type-specific antifibrotic strategies.关键词
肾纤维化/肾小管上皮细胞/转化生长因子β受体Ⅱ型(TGFBR2)/Tgfbr2/单侧输尿管梗阻/Smad3磷酸化/胶原沉积Key words
Renal fibrosis/Tubular epithelial cells/Transforming growth factor-β receptor type Ⅱ(TGFBR2)/Tgfbr2/Unilateral ureteral obstruction/Phosphorylation of Smad3/Collagen deposition引用本文复制引用
HU Lin,YAO Song-yuan..肾小管上皮特异性敲除Tgfbr2抑制Smad3磷酸化减轻UUO小鼠肾纤维化[J].湖北医药学院学报,2025,44(6):703-707,封3,6.
