Abstract
Prolonged hyperglycemia is an important risk factor of the pathogenesis of diabetic retinopathy (DR). Extracellular matrix molecules, such as fibronectin, collagen IV, and laminin, are associated with fibrotic membranes. In this study, we investigated the expression of fibronectin, collagen IV, and laminin in RPE cells under high glucose conditions. Furthermore, we also detected the phosphorylation of protein kinase B (Akt) under high glucose conditions in RPE cells. Our results showed that high glucose upregulated fibronectin, collagen IV, and laminin expression, and activated Akt in RPE cells. We also found that pretreatment with LY294002 (an inhibitor of phosphatidylinositol 3-kinase) abolished high glucose-induced expression of fibronectin, collagen IV, and laminin in RPE cells. Thus, high glucose induced the expression of fibronectin, collagen IV, and laminin through PI3K/Akt signaling pathway in RPE cells, and the PI3K/Akt signaling pathway may contribute to the formation of fibrotic membrane during the development of DR.
Highlights
Diabetic retinopathy (DR) is a major cause of adult blindness globally [1]
Under high glucose condition, strong positive staining of fibronectin, collagen IV, and laminin were observed in the cytosol and nucleus in Retinal pigment epithelial (RPE) cells (Figures 3(a)–3(c))
The expression of extracellular matrix molecules was detected in many organs of diabetes patients and cell types under high glucose conditions [22,23,24,25]
Summary
Diabetic retinopathy (DR) is a major cause of adult blindness globally [1]. Prolonged hyperglycemia plays a vital role in the development of DR. The breakdown of the outer bloodretinal barrier can activate RPE cells, which initiate proliferation and migration and secrete extracellular matrix molecules to combat certain diseases, such as proliferative vitreoretinopathy (PVR) [3], proliferative DR [4], and agerelated macular degeneration (AMD) [5]. The main components of the fibrotic membranes are extracellular matrix molecules, which are combined with some cell types. The PI3K/AKT pathway is important in the development of many diseases and for signaling in normal cells. This pathway plays a key role in numerous cellular functions, including adhesion, proliferation, migration, invasion, metabolism, and survival [8]. We investigate the high glucose-induced expression of extracellular matrix molecules (such as fibronectin, collagen IV, and laminin), the phosphorylation of Akt, and the mechanism involved in the high glucose-induced expression of fibronectin, collagen IV, and laminin in RPE cells
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