Jianing Zhang, Fan Wang, Chang Liu, Xiangyi Lu, Weiping Xu, Yang Yu, Shasha Bai, Zhilian Chen
{"title":"桑孜古本多糖通过 Nrf2 介导的 TGF-β1/Smad7 信号通路调控,减缓糖尿病肾病中的肾上皮-间质转化","authors":"Jianing Zhang, Fan Wang, Chang Liu, Xiangyi Lu, Weiping Xu, Yang Yu, Shasha Bai, Zhilian Chen","doi":"10.1155/2024/3475485","DOIUrl":null,"url":null,"abstract":"<div>\n <p><i>Context</i>. Sanziguben polysaccharides (SZP) have renal protection properties and can reduce renal fibrosis in diabetic nephropathy (DM). However, the mechanism of SZP’s renal protection effect is not yet clear. <i>Objectives</i>. Our study intended to clarify the mechanism of SZP’s renal protection effect in DM. <i>Materials and Methods</i>. In this study, streptozotocin-induced C57BL/6J diabetic nephropathy mice and high glucose combined with TGF-<i>β</i>1-induced EMT in HK-2 cells were used to investigate the effect of Sanziguben polysaccharides. ShRNA-constructed Nrf2 knockdown HK-2 cells were used to explore the role of Nrf2 in Sanziguben polysaccharides inhibiting epithelial-mesenchymal transition. <i>Results</i>. In vivo, the results showed that Sanziguben polysaccharides improved renal epithelial-mesenchymal transition and oxidative stress, and SZP was shown to activate the renal Nrf2, increase Smad7, and inhibit the expression of TGF-<i>β</i>1 (1.05- to 0.71-fold, 1.66- to 0.40-fold and 0.96- to 1.31-fold, respectively). In vitro, SZP ameliorated HK-2 cell epithelial-mesenchymal transition induced by HG combined with TGF-<i>β</i>1, increased the expression of Nrf2 and Smad7, and suppressed the expression of TGF-<i>β</i>1 (1.50- to 1.12-fold, 1.49- to 1.07-fold, and 0.94- to 1.38-fold, respectively). In addition, the above effects of Sanziguben polysaccharides on Nrf2 knockdown HK-2 cells were weakened. <i>Conclusions</i>. The findings suggest that Sanziguben polysaccharides may improve renal epithelial-mesenchymal transition in diabetic nephropathy through Nrf2-mediated regulation of TGF-<i>β</i>1/Smad7 signaling pathway.</p>\n </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/3475485","citationCount":"0","resultStr":"{\"title\":\"Sanziguben Polysaccharides Attenuate Renal Epithelial-Mesenchymal Transition in Diabetic Nephropathy through Nrf2-Mediated Regulation of TGF-β1/Smad7 Signaling Pathway\",\"authors\":\"Jianing Zhang, Fan Wang, Chang Liu, Xiangyi Lu, Weiping Xu, Yang Yu, Shasha Bai, Zhilian Chen\",\"doi\":\"10.1155/2024/3475485\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n <p><i>Context</i>. Sanziguben polysaccharides (SZP) have renal protection properties and can reduce renal fibrosis in diabetic nephropathy (DM). However, the mechanism of SZP’s renal protection effect is not yet clear. <i>Objectives</i>. Our study intended to clarify the mechanism of SZP’s renal protection effect in DM. <i>Materials and Methods</i>. In this study, streptozotocin-induced C57BL/6J diabetic nephropathy mice and high glucose combined with TGF-<i>β</i>1-induced EMT in HK-2 cells were used to investigate the effect of Sanziguben polysaccharides. ShRNA-constructed Nrf2 knockdown HK-2 cells were used to explore the role of Nrf2 in Sanziguben polysaccharides inhibiting epithelial-mesenchymal transition. <i>Results</i>. In vivo, the results showed that Sanziguben polysaccharides improved renal epithelial-mesenchymal transition and oxidative stress, and SZP was shown to activate the renal Nrf2, increase Smad7, and inhibit the expression of TGF-<i>β</i>1 (1.05- to 0.71-fold, 1.66- to 0.40-fold and 0.96- to 1.31-fold, respectively). In vitro, SZP ameliorated HK-2 cell epithelial-mesenchymal transition induced by HG combined with TGF-<i>β</i>1, increased the expression of Nrf2 and Smad7, and suppressed the expression of TGF-<i>β</i>1 (1.50- to 1.12-fold, 1.49- to 1.07-fold, and 0.94- to 1.38-fold, respectively). In addition, the above effects of Sanziguben polysaccharides on Nrf2 knockdown HK-2 cells were weakened. <i>Conclusions</i>. The findings suggest that Sanziguben polysaccharides may improve renal epithelial-mesenchymal transition in diabetic nephropathy through Nrf2-mediated regulation of TGF-<i>β</i>1/Smad7 signaling pathway.</p>\\n </div>\",\"PeriodicalId\":15381,\"journal\":{\"name\":\"Journal of Clinical Pharmacy and Therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/3475485\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Pharmacy and Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1155/2024/3475485\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Pharmacy and Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/2024/3475485","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Sanziguben Polysaccharides Attenuate Renal Epithelial-Mesenchymal Transition in Diabetic Nephropathy through Nrf2-Mediated Regulation of TGF-β1/Smad7 Signaling Pathway
Context. Sanziguben polysaccharides (SZP) have renal protection properties and can reduce renal fibrosis in diabetic nephropathy (DM). However, the mechanism of SZP’s renal protection effect is not yet clear. Objectives. Our study intended to clarify the mechanism of SZP’s renal protection effect in DM. Materials and Methods. In this study, streptozotocin-induced C57BL/6J diabetic nephropathy mice and high glucose combined with TGF-β1-induced EMT in HK-2 cells were used to investigate the effect of Sanziguben polysaccharides. ShRNA-constructed Nrf2 knockdown HK-2 cells were used to explore the role of Nrf2 in Sanziguben polysaccharides inhibiting epithelial-mesenchymal transition. Results. In vivo, the results showed that Sanziguben polysaccharides improved renal epithelial-mesenchymal transition and oxidative stress, and SZP was shown to activate the renal Nrf2, increase Smad7, and inhibit the expression of TGF-β1 (1.05- to 0.71-fold, 1.66- to 0.40-fold and 0.96- to 1.31-fold, respectively). In vitro, SZP ameliorated HK-2 cell epithelial-mesenchymal transition induced by HG combined with TGF-β1, increased the expression of Nrf2 and Smad7, and suppressed the expression of TGF-β1 (1.50- to 1.12-fold, 1.49- to 1.07-fold, and 0.94- to 1.38-fold, respectively). In addition, the above effects of Sanziguben polysaccharides on Nrf2 knockdown HK-2 cells were weakened. Conclusions. The findings suggest that Sanziguben polysaccharides may improve renal epithelial-mesenchymal transition in diabetic nephropathy through Nrf2-mediated regulation of TGF-β1/Smad7 signaling pathway.
期刊介绍:
The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including:
Rational therapeutics
Evidence-based practice
Safety, cost-effectiveness and clinical efficacy of drugs
Drug interactions
Clinical impact of drug formulations
Pharmacogenetics
Personalised, stratified and translational medicine
Clinical pharmacokinetics.