Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USA.
Cell Signal. 2020 Sep;73:109687. doi: 10.1016/j.cellsig.2020.109687. Epub 2020 Jun 1.
High mobility group box 1 (HMGB1) is a key player in retinal inflammation. HMGB1 is a danger associated protein pattern receptor which can sense high glucose as a stressor. Increased HMGB1 levels have been found in patients with late stage diabetic retinopathy. HMGB1 can bind toll-like receptor 4 (TLR4) and the receptor for advanced glycation end-products (RAGE), leading to increased inflammation commonly through nuclear factor kappa beta (NFkB). Because diabetic patients have been found to have increased HMGB1 and RAGE levels, as well as polymorphisms of TLR4, a number of investigations have focused on inhibition of these pathways in the diabetic retina. Work in diabetic animal models and cell culture have demonstrated a number of factors that can inhibit HMGB1/TLR4/RAGE signaling. This regulation offers potential new avenues for therapeutic development. This review is focused on HMGB1 signaling and downstream pathways leading to inflammation in the diabetic retina.
高迁移率族蛋白 B1（HMGB1）是视网膜炎症的关键参与者。HMGB1 是一种危险相关蛋白模式受体，可作为应激源感应高血糖。晚期糖尿病性视网膜病变患者的 HMGB1 水平升高。HMGB1 可以与 Toll 样受体 4（TLR4）和晚期糖基化终产物受体（RAGE）结合，导致炎症增加，通常通过核因子 kappa beta（NFkB）。由于已发现糖尿病患者的 HMGB1 和 RAGE 水平以及 TLR4 的多态性增加，因此许多研究都集中在抑制糖尿病视网膜中的这些途径上。在糖尿病动物模型和细胞培养中的研究表明，有许多因素可以抑制 HMGB1/TLR4/RAGE 信号。这种调节为治疗开发提供了新的潜在途径。这篇综述主要关注 HMGB1 信号及其下游途径导致糖尿病视网膜炎症。
