Autophagy Modulates the Migration of Retinal Pericytes Induced by Advanced Glycation End Products

Abstract

Retinal pericyte migration occurs in the early stage of diabetic retinopathy (DR), which is one of the important causes of pericyte loss. Autophagy has been found to play essential roles in the regulation of many types of cell migration. In this study, we explored the relationship between autophagy and retinal pericyte migration. In diabetic rats, the retinas became thinner, and the level of autophagy in each cell layer increased. In the primary culture of bovine retinal pericytes, we found that advanced glycation end products (AGEs) increased the migratory cell ability without influencing cell viability, which also increased the phosphorylation of focal adhesion kinase (FAK) and the expression of matrix metalloproteinase (MMP)-2 and decreased the expression of vinculin. AGEs-induced retinal pericyte autophagy and the inhibition of autophagy with chloroquine significantly inhibited cell migration, reversed AGEs-induced FAK phosphorylation, and changed vinculin and MMP-2 protein expression. These results provide a new insight into the migration mechanism of retinal pericytes. The early control of autophagy has a potential effect on regulating pericyte migration, which may contribute to keeping the integrity of retinal vessels in DR.

Role of autophagy in angiogenic potential of vascular pericytes

“…Previous data have confirmed the inevitable role of autophagy on bovine retinal pericyte migration in in vitro conditions ( Lin et al, 2022 ). The exposure of bovine retinal pericytes to advanced glycation end products (AGEs) led to autophagy activity (LC3-II/LC3-I ratio↑, and P62↓) and enhanced migration properties without changes in the survival rate.…”

“…The exposure of bovine retinal pericytes to advanced glycation end products (AGEs) led to autophagy activity (LC3-II/LC3-I ratio↑, and P62↓) and enhanced migration properties without changes in the survival rate. In retinal pericytes, the production of metalloproteinase-2 (MMP-2) and phosphorylation of focal adhesion kinase (FAK) were elevated ( Lin et al, 2022 ). Of note, incubation of these cells with chloroquine, an autophagy inhibitor, can blunt the increase of FAK and MMP-2.…”

“…Direct evidence for the reduction of focal adhesion stability in pericytes exists when autophagic NBR1 is induced in an AMPK-dependent manner. These apparent morphological changes can increase the leakage of BBB and retinal vessels under diabetic conditions ( Lin et al, 2022 ). Owing to its protective properties, autophagy can protect different cell types after exposure to several insults, however, it has been proposed that the over-activation of autophagic machinery can mediate cell dysfunction and kill the cells in severe situations ( Rezabakhsh et al, 2017 ).…”

Impaired pulp healing associated with underlying disorders in the dental pulp of rats with type 2 diabetes

“…This indicated that the thickening of collagen fibers may be partially a compensatory response to AGE. 36 Studies have reported that AGE can directly cross-link with vascular BM proteins and lead to BM thickening; 33 ; AGE in ECs and pericytes can directly impair the conformation and function of intracellular proteins, and result in endothelial dysfunction; 33 , 37 ; AGE can exert a stimulatory role in endothelial cell production of VEGF, which is involved in the development of diabetic retinopathy. 33 These suggested that vasculopathy in the diabetic pulp may be attributable to the AGE accumulation.…”

Vinculin Identified as a Potential Biomarker in Hand-Arm Vibration Syndrome Based on iTRAQ and LC–MS/MS-Based Proteomic Analysis

“…It participated in the signal transition from focal adhesion to conditional cytoskeleton dynamics . Conversely, the migratory cell ability is accompanied by a decrease in vinculin expression . In recent years, the downregulation of vinculin has been found in several highly metastatic cancer cells, which reminded us of its unique role in metastasis and relapse. − However, few efforts about vinculin were made in occupational diseases; the vinculin expression level in plasma has not been studied thoroughly compared with other tissues or cells, either.…”