FoxO_4与糖尿病及其并发症的研究进展

FoxO_4 in diabetes and its complications

越来越多的证据证实,叉头转录因子(Fox)家族成员之一——叉头"其他"蛋白(FoxO)在胰岛素和生长因子调节细胞增生、凋亡和代谢中具有重要意义。鉴于FoxO的传导通路及其组织分布与代谢的密切关系,FoxO在糖尿病及其并发症发病机制中扮演的角色成为研究热点。本文主要介绍FoxO家族成员FoxO4相关的分子生物学、遗传学及其与糖尿病及其并发症的关系,从而为FoxO4在糖尿病及其并发症的发生发展中作用的研究提供参考。

An increasing number of evidences illustrates that FoxO a class of the Fox （forkhead transcription factors） family involves in a series of vital cellular activities conducted by insulin and other growth factors, such as cellular proliferation, apoptosis, metabolism. FoxO4, a member of FoxO family, is attractive for strategies of new pharmaceutical agents against diabetes mellitus （DM）. Here, we mainly focus on FoxO4, which is highly expressed in heart, muscle and adipose tissues. When activated, it can affect a variety of processes, including tumor suppression, longevity, development and metabolism. FoxO4 participates in the progression of diabetes and its vascular complications. It also inhibits the late steps of cholesterol biosynthesis and thus enhances basal glucose uptake and triacylglycerol accumulation. The ingested glucose can be cleared rapidly in FoxO4-overexpressed mice. While cultured murine podocytes were exposed to AGE-BSA（advanced glycation end products-bovine serum albumin）, the expression of Bim/Bcl2111, an effector protein of apoptosis, was increased in relation to FoxO4 transcriptional activation. In atherosclerogenesis （AS）, FoxO4 plays an important role mainly by promoting smooth muscle cell（SMC） migration and inhibiting the activity of myocardin to repress SMC differentiation via AGE-BSA induced heparanase expression. In addition, in vivo, FoxO4 could impact cardiovascular complications of diabetes through bone marrow derived ceils. In summary, FoxO4 takes part in the complex development and progression of diabetes and its complications, further studies on it will help us better understand the possible mechanisms and may offer a new therapeutic target for preventing this world-wide disease and its complications.