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对FOXO在糖尿病视网膜病变中作用的机制性见解。

Mechanistic insights into the role of FOXO in diabetic retinopathy.

作者信息

Behl Tapan, Wadhwa Muskan, Sehgal Aayush, Singh Sukhbir, Sharma Neelam, Bhatia Saurabh, Al-Harrasi Ahmed, Aleya Lotfi, Bungau Simona

机构信息

Chitkara College of Pharmacy, Chitkara University Punjab 140401, India.

Natural & Medical Sciences Research Centre, University of Nizwa Nizwa 342001, Oman.

出版信息

Am J Transl Res. 2022 Jun 15;14(6):3584-3602. eCollection 2022.

Abstract

Diabetes mellitus (DM), a metabolic disorder characterized by insulin-deficiency or insulin-resistant conditions. The foremost microvascular complication of diabetes is diabetic retinopathy (DR). This is a multifaceted ailment mainly caused by the enduring adverse effects of hyperglycaemia. Inflammation, oxidative stress, and advanced glycation products (AGES) are part and parcel of DR pathogenesis. In regulating many cellular and biological processes, the family of fork-head transcription factors plays a key role. The current review highlights that FOXO is a requisite regulator of pathways intricate in diabetic retinopathy on account of its effect on microvascular cells inflammatory and apoptotic gene expression, and FOXO also has the foremost province in regulating cell cycle, proliferation, apoptosis, and metabolism. Blockage of insulin turns into an exaggerated level of glucose in the bloodstream and can upshot into the exaggerated triggering of FOXO1, which can ultimately uplift the production of several factors of apoptosis and inflammation, such as TNF-α, NF-kB, and various others, as well as reactive oxygen species, which can also come up with diabetic retinopathy. The current review also focuses on various therapies which can be used in the future, like SIRT1 signalling, resveratrol, retinal VEGF, etc., which can be used to suppress FOXO over activation and can prevent the progression of diabetic complications viz. diabetic retinopathy.

摘要

糖尿病(DM)是一种以胰岛素缺乏或胰岛素抵抗为特征的代谢紊乱疾病。糖尿病最主要的微血管并发症是糖尿病视网膜病变(DR)。这是一种多方面的疾病,主要由高血糖的长期不良影响引起。炎症、氧化应激和晚期糖基化终产物(AGES)是DR发病机制的重要组成部分。在调节许多细胞和生物学过程中,叉头转录因子家族起着关键作用。当前的综述强调,FOXO是糖尿病视网膜病变复杂途径的必要调节因子,因为它对微血管细胞炎症和凋亡基因表达有影响,并且FOXO在调节细胞周期、增殖、凋亡和代谢方面也起着最重要的作用。胰岛素的阻断会导致血液中葡萄糖水平升高,并可能导致FOXO1过度激活,这最终会提高几种凋亡和炎症因子的产生,如肿瘤坏死因子-α、核因子-κB等,以及活性氧,这也可能导致糖尿病视网膜病变。当前的综述还关注了未来可以使用的各种疗法,如SIRT1信号通路、白藜芦醇、视网膜血管内皮生长因子等,这些疗法可以用来抑制FOXO的过度激活,并可以预防糖尿病并发症即糖尿病视网膜病变的进展。

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