Secreted Protein Acidic and Rich in Cysteine Mediates the Development and Progression of Diabetic Retinopathy

Abstract

BackgroundsDiabetic retinopathy (DR) is one of the most severe microvascular complications of diabetes mellitus (DM). Secreted protein acidic and rich in cysteine (SPARC) has been found to play an important role in many diseases, but its role and mechanism in DR remain unknown.MethodsWe studied the role of SPARC and integrin β1 in vascular pathophysiology and identified potential therapeutic translation. The SPARC levels were tested in human serum and vitreous by ELISA assay, and then the Gene Expression Omnibus (GEO) dataset was used to understand the key role of the target gene in DR. In human retinal capillary endothelial cells (HRCECs), we analyzed the mRNA and protein level by RT-PCR, immunohistochemistry, and Western blotting. The cell apoptosis, cell viability, and angiogenesis were analyzed by flow cytometry, CCK-8, and tube formation.ResultsIn this study, we investigated the role of SPARC in the development and progression of human DR and high glucose-induced HRCEC cells and found that the SPARC-ITGB1 signaling pathway mimics early molecular and advanced neurovascular pathophysiology complications of DR. The result revealed that DR patients have a high-level SPARC expression in serum and vitreous. Knockdown of SPARC could decrease the expressions of inflammatory factors and VEGFR, inhibit cell apoptosis and angiogenesis, and increase cell viability by regulating integrin β1 in HRCECs.ConclusionSPARC promotes diabetic retinopathy via the regulation of integrin β1. The results of this study can provide a potential therapeutic application for the treatment of DR.

Extracellular matrix‐related and serine protease proteins in the amniotic fluid of women with early preterm labor: Association with spontaneous preterm birth, intra‐amniotic inflammation, and microbial invasion of the amniotic cavity

“…81,82 This molecule is involved in the pathogenesis of several inflammatory diseases, including ulcerative colitis, diabetic retinopathy, and hemarthrosis. [83][84][85] To the best of our knowledge, in the obstetric field, only one study by McParland et al evaluated the effect of SPARC expression on the cleavage and rupture of fetal membranes at term and showed that the expression pattern of SPARC was primarily restricted to the fetal membranes overlying the cervix in the lower uterine segment prior to and during labor and within the rupture tear after delivery. 86 However, no study has focused specifically on the association between SPARC, IAI/MIAC, and SPTB.…”

“…In particular, SPARC exerts anti‐inflammatory responses via a negative regulation of nuclear factor‐kB and tumor necrosis factor (TNF)‐β signaling 81,82 . This molecule is involved in the pathogenesis of several inflammatory diseases, including ulcerative colitis, diabetic retinopathy, and hemarthrosis 83–85 . To the best of our knowledge, in the obstetric field, only one study by McParland et al.…”

Adipose Tissue Paracrine-, Autocrine-, and Matrix-Dependent Signaling during the Development and Progression of Obesity

“…It was shown that leptin induces SPARC expression in adipose tissue and that SPARC expression was then correlated with IL-6 and fasting insulin levels [150]. SPARC has also been shown to further retinopathy in individuals with diabetes by interacting with VEGF and PAI-1 in endothelial cells [151]. In a 3D in vitro vasculature model, leptin was also shown to have profibrotic effects, indicated by the upregulation of collagens II and IV and the downregulation of MMPs 2 and 9 [28,80].…”

The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials

“…Overexpression of SPARC is capable of disrupting the integrity of vascular endothelial cell layers, affecting matrix composition and cell adhesion, thus facilitating the invasion and metastasis of tumors (106,108,109). SPARC knockdown reduces the expression levels of inflammatory factors and VEGFR, downregulating ECs apoptosis, and angiogenesis in diabetic retinopathy (110). SPARC is a key factor in angiogenesis and endothelial barrier function which is well established; however, the underlying mechanism of RA-induced angiogenesis has not yet been defined.…”