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mTOR信号通路:糖尿病肾病进展中的关键因素及治疗靶点。

mTOR pathway: A key player in diabetic nephropathy progression and therapeutic targets.

作者信息

Shi Jingxuan, Liu Xinze, Jiao Yuanyuan, Tian Jingwei, An Jiaqi, Zou Guming, Zhuo Li

机构信息

Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.

China-Japan Friendship Institute of Clinical Medical Sciences, Beijing 100029, China.

出版信息

Genes Dis. 2024 Mar 8;12(2):101260. doi: 10.1016/j.gendis.2024.101260. eCollection 2025 Mar.

Abstract

Diabetic nephropathy is a prevalent complication of diabetes and stands as the primary contributor to end-stage renal disease. The global prevalence of diabetic nephropathy is on the rise, however, due to its intricate pathogenesis, there is currently an absence of efficacious treatments to enhance renal prognosis in affected patients. The mammalian target of rapamycin (mTOR), a serine/threonine protease, assumes a pivotal role in cellular division, survival, apoptosis delay, and angiogenesis. It is implicated in diverse signaling pathways and has been observed to partake in the progression of diabetic nephropathy by inhibiting autophagy, promoting inflammation, and increasing oxidative stress. In this academic review, we have consolidated the understanding of the pathological mechanisms associated with four distinct resident renal cell types (podocytes, glomerular mesangial cells, renal tubular epithelial cells, and glomerular endothelial cells), as well as macrophages and T lymphocytes, within a diabetic environment. Additionally, we highlight the research progress in the treatment of diabetic nephropathy with drugs and various molecules interfering with the mTOR signaling pathway, providing a theoretical reference for the treatment and prevention of diabetic nephropathy.

摘要

糖尿病肾病是糖尿病常见的并发症,也是终末期肾病的主要原因。全球糖尿病肾病的患病率正在上升,然而,由于其发病机制复杂,目前缺乏有效的治疗方法来改善受影响患者的肾脏预后。雷帕霉素靶蛋白(mTOR)是一种丝氨酸/苏氨酸蛋白酶,在细胞分裂、存活、凋亡延迟和血管生成中起关键作用。它参与多种信号通路,并且已观察到通过抑制自噬、促进炎症和增加氧化应激参与糖尿病肾病的进展。在这篇学术综述中,我们综合了对糖尿病环境中四种不同的肾固有细胞类型(足细胞、肾小球系膜细胞、肾小管上皮细胞和肾小球内皮细胞)以及巨噬细胞和T淋巴细胞相关病理机制的理解。此外,我们强调了用药物和各种干扰mTOR信号通路的分子治疗糖尿病肾病的研究进展,为糖尿病肾病的治疗和预防提供理论参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e69d/11665407/9c42d1770f33/gr1.jpg

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