Heat shock protein 70 promotes the progression of type 2 diabetic nephropathy by inhibiting T-cell immunoglobulin and mucin domain-3 and thereby promoting Th17/Treg imbalance.

IF 2.4 4区医学 Q2 UROLOGY & NEPHROLOGY Nephrology Pub Date : 2024-12-01 Epub Date: 2024-10-21 DOI:10.1111/nep.14396

Juntai Zhang, Yan Cai, Yan Qin, Jie Liu, Jie Ding, Mengying Xu, Li Yang, Yuanxin Zheng, Xi Zhang

{"title":"Heat shock protein 70 promotes the progression of type 2 diabetic nephropathy by inhibiting T-cell immunoglobulin and mucin domain-3 and thereby promoting Th17/Treg imbalance.","authors":"Juntai Zhang, Yan Cai, Yan Qin, Jie Liu, Jie Ding, Mengying Xu, Li Yang, Yuanxin Zheng, Xi Zhang","doi":"10.1111/nep.14396","DOIUrl":null,"url":null,"abstract":"Aim: Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. We aimed to investigate the role of regulatory T cells (Tregs) and helper T cells 17 (Th17) in the development and progression of DN.Methods: A mouse type 2 diabetic nephropathy (T2DN) model was established. Immunohistochemistry was used to detect the expression of HSP70 and Tim-3 in mouse kidney tissues, and western blotting was used to detect the expression levels of HSP70 and Tim-3. PAS staining and Masson's trichrome staining were used to detect the degree of kidney injury. Flow cytometry was used to detect the number of Th17 and Treg cells in blood and kidney tissues. The expression levels of interleukin 17 (IL-17) and interleukin 10 (IL-10) in the serum were measured via ELISA.Results: The expression of HSP70 was significantly increased while the expression of Tim-3 was significantly decreased in the kidneys of mice in the T2DN group compared with those in the control (NC) group. Additionally, the inhibition of HSP70 upregulated the expression of Tim-3 in T2DN mice. The Th17/Treg ratio was significantly greater in the blood and kidneys of the mice in the T2DN group than in those of the NC group, the expression of serum IL-17 was increased, and the expression of IL-10 was decreased.Conclusion: Increased HSP70 inhibits Tim-3 expression in T2DN mouse kidney tissues, and subsequently causes a Th17/Treg imbalance and an inflammatory response, ultimately leading to kidney injury. The inhibition of HSP70 may alleviate the progression of T2DN.","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":" ","pages":"806-814"},"PeriodicalIF":2.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/nep.14396","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/21 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Aim: Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. We aimed to investigate the role of regulatory T cells (Tregs) and helper T cells 17 (Th17) in the development and progression of DN.

Methods: A mouse type 2 diabetic nephropathy (T2DN) model was established. Immunohistochemistry was used to detect the expression of HSP70 and Tim-3 in mouse kidney tissues, and western blotting was used to detect the expression levels of HSP70 and Tim-3. PAS staining and Masson's trichrome staining were used to detect the degree of kidney injury. Flow cytometry was used to detect the number of Th17 and Treg cells in blood and kidney tissues. The expression levels of interleukin 17 (IL-17) and interleukin 10 (IL-10) in the serum were measured via ELISA.

Results: The expression of HSP70 was significantly increased while the expression of Tim-3 was significantly decreased in the kidneys of mice in the T2DN group compared with those in the control (NC) group. Additionally, the inhibition of HSP70 upregulated the expression of Tim-3 in T2DN mice. The Th17/Treg ratio was significantly greater in the blood and kidneys of the mice in the T2DN group than in those of the NC group, the expression of serum IL-17 was increased, and the expression of IL-10 was decreased.

Conclusion: Increased HSP70 inhibits Tim-3 expression in T2DN mouse kidney tissues, and subsequently causes a Th17/Treg imbalance and an inflammatory response, ultimately leading to kidney injury. The inhibition of HSP70 may alleviate the progression of T2DN.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

热休克蛋白 70 可抑制 T 细胞免疫球蛋白和粘蛋白结构域-3，从而促进 Th17/Treg 失衡，从而促进 2 型糖尿病肾病的进展。

目的：糖尿病肾病（DN）是糖尿病最常见的并发症。我们旨在研究调节性 T 细胞（Tregs）和辅助性 T 细胞 17（Th17）在 DN 的发生和发展中的作用：方法：建立小鼠 2 型糖尿病肾病（T2DN）模型。免疫组化法检测小鼠肾组织中 HSP70 和 Tim-3 的表达，Western 印迹法检测 HSP70 和 Tim-3 的表达水平。PAS染色和Masson三色染色用于检测肾脏损伤程度。流式细胞术用于检测血液和肾组织中 Th17 和 Treg 细胞的数量。通过 ELISA 检测血清中白细胞介素 17（IL-17）和白细胞介素 10（IL-10）的表达水平：结果：与对照（NC）组相比，T2DN 组小鼠肾脏中 HSP70 的表达明显增加，而 Tim-3 的表达明显减少。此外，抑制 HSP70 会上调 T2DN 小鼠 Tim-3 的表达。T2DN组小鼠血液和肾脏中的Th17/Treg比例明显高于NC组，血清IL-17的表达增加，IL-10的表达减少：结论：HSP70的增加抑制了T2DN小鼠肾组织中Tim-3的表达，进而引起Th17/Treg失衡和炎症反应，最终导致肾损伤。抑制 HSP70 可能会缓解 T2DN 的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Nephrology 医学-泌尿学与肾脏学

CiteScore

4.50

自引率

4.00%

发文量

128

审稿时长

4-8 weeks

期刊介绍： Nephrology is published eight times per year by the Asian Pacific Society of Nephrology. It has a special emphasis on the needs of Clinical Nephrologists and those in developing countries. The journal publishes reviews and papers of international interest describing original research concerned with clinical and experimental aspects of nephrology.