Exercise alleviates renal interstitial fibrosis by ameliorating the Sirt1-mediated TGF-β1/Smad3 pathway in T2DM mice.

IF 2.6 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Endocrine Connections Pub Date : 2024-02-23 Print Date: 2024-03-01 DOI:10.1530/EC-23-0448

Xianghe Chen, Xinyu Zeng, Xiao Qiu, Chi Liu, Pengcheng Lu, Ziming Shen, Xiangxiang Zhou, Kang Yang

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Abstract

Background: Renal interstitial fibrosis is the pathophysiological basis of type 2 diabetes mellitus (T2DM). Exercise appears to improve kidney interstitial fibrosis in T2DM, in which silent information regulator factor 2-related enzyme 1 (Sirt1) is a critical regulator. However, the role of Sirt1 in mediating exercise on renal tissue as well as its mechanism remains unknown.

Methods: T2DM mouse models were created using a high-fat diet mixed with streptozotocin, followed by 8 weeks of treadmill exercise and niacinamide (Sirt1 inhibitor) intervention. Kits for detecting biochemical indices of renal function were used. The pathological appearance and severity of renal tissue were examined using hematoxylin and eosin, Masson and immunohistochemical staining. The mRNA and protein expression of relevant signaling pathway factors were determined to use real-time reverse transcriptase-polymerase chain reaction and western blotting.

Results: T2DM can promote renal interstitial fibrosis, increase kidney index, serum creatinine, blood urea nitrogen and 24 h urinary total protein and cause pathological changes in renal tissue and affect renal function. After 8 weeks of exercise intervention, the biochemical indicators in the kidney of T2DM mice were decreased, Sirt1 expression was increased, the expression of TGF-β1, Smad3, collagen type I (COL1) and collagen type III (COL3) were decreased, and the renal interstitial fibrosis, renal tissue structural lesions and renal function were improved. However, after the nicotinamide intervention, renal interstitial fibrosis of T2DM mice was aggravated, and the improvement effect of exercise on renal interstitial fibrosis of T2DM mice was abolished.

Conclusion: The upregulation of Sirt1 expression by exercise can inhibit the transforming growth factor β1/Smad3 pathway, thereby inhibiting the expression and deposition of COL1 and COL3 in renal interstitium, thereby improving renal interstitial fibrosis in T2DM.

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通过改善 Sirt1 介导的 TGF-β1/Smad3 通路，运动可减轻 T2DM 小鼠的肾间质纤维化。

背景：肾间质纤维化是 T2DM 的病理生理基础：肾间质纤维化是 T2DM 的病理生理基础。运动似乎能改善 T2DM 患者的肾间质纤维化，而 Sirt1 是肾间质纤维化的关键调节因子。然而，Sirt1 在介导运动对肾组织的作用及其机制仍不清楚：方法：通过高脂饮食与链脲佐菌素混合，然后进行为期 8 周的跑步机运动和烟酰胺（Sirt1 抑制剂）干预，建立了 T2DM 小鼠模型。实验中使用了检测肾功能生化指标的试剂盒。使用 HE、Masson 和免疫组化染色法检测肾组织的病理外观和严重程度。采用 RT-PCR 和 Western 印迹法测定相关信号通路因子的 mRNA 和蛋白表达：结果：T2DM可促进肾间质纤维化，增加KI、SCr、BUN和24h UTP，引起肾组织病理变化，影响肾功能。运动干预8周后，T2DM小鼠肾脏生化指标下降，Sirt1表达增加，TGF-β1、Smad3、COL1和COL3表达下降，肾间质纤维化、肾组织结构病变和肾功能得到改善。但烟酰胺干预后，T2DM小鼠肾间质纤维化加重，运动对T2DM小鼠肾间质纤维化的改善作用消失：结论：运动上调Sirt1的表达可抑制TGF-β1/Smad3通路，从而抑制COL1和COL3在肾间质的表达和沉积，从而改善T2DM小鼠肾间质纤维化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine Connections Medicine-Internal Medicine

CiteScore

5.00

自引率

3.40%

发文量

361

审稿时长

6 weeks

期刊介绍： Endocrine Connections publishes original quality research and reviews in all areas of endocrinology, including papers that deal with non-classical tissues as source or targets of hormones and endocrine papers that have relevance to endocrine-related and intersecting disciplines and the wider biomedical community.