WISP-1对肾纤维化大鼠肾小管上皮细胞纤维化的影响

doi:10.16352/j.issn.1001-6325.2025.04.0471

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (4): 471-477.doi: 10.16352/j.issn.1001-6325.2025.04.0471

WISP-1对肾纤维化大鼠肾小管上皮细胞纤维化的影响

杨二梅^*, 夏薇青, 宋培, 严佳

石家庄市第三医院肾内科,河北石家庄 050011

收稿日期:2024-09-12 修回日期:2024-12-31 出版日期:2025-04-05 发布日期:2025-03-24
通讯作者: ^*yyyy1602@163.com
基金资助:
2021年河北省医学科学研究重点课题计划(20210528)

Effect of WISP-1 on fibrosis of renal tubular epithelial cell in rats with renal fibrosis

YANG Ermei^*, XIA Weiqing, SONG Pei, YAN Jia

Department of Nephrology, the Third Hospital of Shijiazhuang, Shijiazhuang 050011, China

Received:2024-09-12 Revised:2024-12-31 Online:2025-04-05 Published:2025-03-24

摘要/Abstract

摘要： 目的　探究Wnt分泌蛋白1(WISP-1)对肾纤维化大鼠肾小管上皮细胞纤维化的影响及机制。方法　选取24只成年大鼠及大鼠肾小管上皮细胞系(NEK-52E),分别进行体内及体外实验。大鼠随机分为对照组及研究组,采用单侧输尿管闭塞手术构建体内肾纤维化模型,研究组使用WISP-1/CCN4 亲和纯化的单克隆抗体注射阻断肾脏WISP-1表达;细胞系培养后诱导纤维化,分别给予WISP-1过表达及抑制处理,采用组织学和免疫组织化学检测肾脏大鼠病理学变化,使用Western法及RT-qPCR法检测纤维化相关指标。结果　WISP-1过表达胶原蛋白Ⅰ(Col Ⅰ)、纤连蛋白(FN)、转化生长因子-β1(TGF-β1)蛋白及mRNA高于对照,WISP-1抑制Col Ⅰ、FN、TGF-β1蛋白及mRNA低于对照(P＜0.05); WISP-1 阻断给药减弱肾纤维化其病理变化。研究组Col Ⅰ、FN、α平滑肌肌动蛋白(α-SMA)、TGF-β1蛋白及mRNA、LC3、Beclin-1蛋白低于对照组,泛素结合蛋白p62(SQSTM1/p62)高于对照组(P＜0.05)。WISP-1抑制剂LC3、Beclin-1的表达低于对照组, SQSTM1/p62 的表达高于对照组,WISP-1过表达组LC3 和 Beclin-1的表达高于对照组, SQSTM1/p62 的表达低于对照组。结论　WISP-1过表达促进大鼠肾小管上皮细胞纤维化, 增强TGF-β1介导的自噬可能是肾纤维化的机制之一。

关键词: Wnt分泌蛋白1, 慢性肾脏病, 肾纤维化, 作用机制

Abstract: Objective To investigate the effect and mechanism of WISP-1 on renal tubular epithelial cell fibrosis in rats with renal fibrosis. Methods Twenty-four adult rats and renal tubular epithelial cell line(NEK-52E) were selected for in vivo and in vitro experiments. The rats were randomly divided into control group and study group, and the in vivo renal fibrosis model was established. The expression of WISP-1 in the study group was blocked. The cell lines were induced to fibrosis followed by WISP-1 over-expression or inhibition. The related indicators of fibrosis were observed. Results Protein and mRNA level of Collagen Ⅰ(Col Ⅰ), fibronectin (FN), transforming growth factor-β1(TGF-β1) in WISP-1 over-expression group were all higher than those in control group. The protein and mRNA level of Col Ⅰ, FN and TGF-β1 in the WISP-1 inhibition group were lower than those in the control group(P＜0.05). WISP-1 blockade attenuated the pathological changes of renal fibrosis. The protein and mRNA levels of Col Ⅰ, FN, α-smooth muscle actin(α-SMA), TGF-β1, LC3 and Beclin-1 in the study group were lower than those in the control group, and the level of ubiquitin binding protein p62(SQSTM1/p62) was higher than that in the control group(P＜0.05). The expression of LC3 and Beclin-1 in WISP-1 inhibitor group was lower than that in the control group and the expression of SQSTM1/p62 was higher than that in the control group. The expression of LC3 and Beclin-1 in the WISP-1 over-expression group was higher than that in the control group, and the expression of SQSTM1/p62 was lower than that in the control group. Conclusions Overexpression of WISP-1 promotes the fibrosis of rat renal tubular epithelial cells, and enhanced TGF-β1-mediated autophagy might be a underlying mechanism to mediate renal fibrosis.

Key words: WISP-1, chronic kidney disease, renal fibrosis, mechanism of action

中图分类号:

R363

杨二梅, 夏薇青, 宋培, 严佳. WISP-1对肾纤维化大鼠肾小管上皮细胞纤维化的影响[J]. 基础医学与临床, 2025, 45(4): 471-477.

YANG Ermei, XIA Weiqing, SONG Pei, YAN Jia. Effect of WISP-1 on fibrosis of renal tubular epithelial cell in rats with renal fibrosis[J]. Basic & Clinical Medicine, 2025, 45(4): 471-477.

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WISP-1对肾纤维化大鼠肾小管上皮细胞纤维化的影响

Effect of WISP-1 on fibrosis of renal tubular epithelial cell in rats with renal fibrosis

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