Hispolon reduces mitochondrial dysfunction and improves fibrosis of diabetes nephropathy by activating AMPK signal and inhibiting mPTP opening

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-09-11 DOI:10.1016/j.cellsig.2025.112130

Yapeng Wang , Ajau Danis , Xueyi Wang , Jia Ren , Teng Ma , Ruixiao Wang

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引用次数: 0

Abstract

Diabetic nephropathy progression is linked to the AMPK/SIRT1/PGC-1α signaling pathway. Hispolon's potential in improving mitochondrial function and treating diabetic nephropathy via this pathway was unclear. This study used db/db mice and high glucose-induced SV40 MES 13 cells to explore Hispolon's renoprotective mechanisms.

In vivo, db/db mice showed glomerular damage, collagen deposition, glycoprotein accumulation, and elevated serum creatinine and urea nitrogen. Hispolon intervention improved these features and parameters. It reduced renal MDA levels, enhanced SOD activity, suppressed pro-inflammatory mediators, and downregulated fibrosis markers. Western blot analysis showed Hispolon restored p-AMPK, SIRT1, and PGC-1α protein levels. In vitro, Hispolon enhanced cell viability, inhibited apoptosis, and reversed high glucose-induced oxidative stress and inflammation in SV40 MES 13 cells. It improved mitochondrial energy metabolism by restoring mitochondrial membrane potential, increasing ATP production, and inhibiting abnormal mPTP opening. Mechanistic studies confirmed that the AMPK/SIRT1/PGC-1α signaling cascade is key for Hispolon's regulation of mPTP dynamics. In conclusion, Hispolon slows diabetic nephropathy progression by activating the AMPK/SIRT1/PGC-1α pathway, inhibiting mPTP opening, and improving mitochondrial dysfunction.

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Hispolon通过激活AMPK信号和抑制mPTP开放，减少线粒体功能障碍，改善糖尿病肾病纤维化。

糖尿病肾病的进展与AMPK/SIRT1/PGC-1α信号通路有关。Hispolon在改善线粒体功能和通过这一途径治疗糖尿病肾病方面的潜力尚不清楚。本研究使用db/db小鼠和高糖诱导的SV40 MES 13细胞来探索Hispolon的肾保护机制。在体内，db/db小鼠出现肾小球损伤，胶原沉积，糖蛋白积累，血清肌酐和尿素氮升高。Hispolon干预改善了这些特征和参数。它降低肾脏MDA水平，增强SOD活性，抑制促炎介质，下调纤维化标志物。Western blot分析显示，Hispolon恢复了p-AMPK、SIRT1和PGC-1α蛋白水平。在体外，Hispolon可提高SV40 MES 13细胞的细胞活力，抑制细胞凋亡，逆转高糖诱导的氧化应激和炎症。它通过恢复线粒体膜电位、增加ATP的产生和抑制异常mPTP开放来改善线粒体能量代谢。机制研究证实AMPK/SIRT1/PGC-1α信号级联是Hispolon调控mPTP动力学的关键。总之，Hispolon通过激活AMPK/SIRT1/PGC-1α通路、抑制mPTP开放和改善线粒体功能障碍来减缓糖尿病肾病的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.