Abstract

Tumor necrosis factor-like weak inducer of apoptosis association with proliferative diabetic retinopathy and promotes proliferation and collagen synthesis in retinal ARPE-19 cells

Chronic inflammation develops in the retinal microvasculature under sustained hyperglycemia and is implicated in the pathogenesis of diabetic retinopathy. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 have been reported to promote pro-inflammatory cytokines, which are involved in the pathogenesis of proliferative diabetic retinopathy (PDR). It is therefore possible that the TWEAK/Fn14 pathway can play a regulatory role in PDR. In the present study, we examined the expression of TWEAK and Fn14 in vitreous fluid from PDR patients. To confirm the correlation between the TWEAK expression and clinical pathological characteristics of PDR, we investigated the regulatory role of the TWEAK/Fn14 pathway in cell proliferation and collagen synthesis in retinal ARPE-19 cells. The results demonstrated that vitreous fluid from patients with PDR had higher levels of TWEAK and Fn14 than that from T2DM patients without PDR, thus suggesting an important regulatory role of TWEAK/Fn14 signaling in the pathogenesis of PDR. Furthermore, overexpression of TWEAK in ARPE-19 cells also promoted proliferation of and collagen synthesis in these retinal cells. It is possible that TWEAK/Fn14 upregulation in PDR may contribute to PDR progression by promoting the proliferation or fibrosis of retinal cells. Chronic inflammation develops in the retinal microvasculature under sustained hyperglycemia and is implicated in the pathogenesis of diabetic retinopathy. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 have been reported to promote pro-inflammatory cytokines, which are involved in the pathogenesis of proliferative diabetic retinopathy (PDR). It is therefore possible that the TWEAK/Fn14 pathway can play a regulatory role in PDR. In the present study, we examined the expression of TWEAK and Fn14 in vitreous fluid from PDR patients. To confirm the correlation between the TWEAK expression and clinical pathological characteristics of PDR, we investigated the regulatory role of the TWEAK/Fn14 pathway in cell proliferation and collagen synthesis in retinal ARPE-19 cells. The results demonstrated that vitreous fluid from patients with PDR had higher levels of TWEAK and Fn14 than that from T2DM patients without PDR, thus suggesting an important regulatory role of TWEAK/Fn14 signaling in the pathogenesis of PDR. Furthermore, overexpression of TWEAK in ARPE-19 cells also promoted proliferation of and collagen synthesis in these retinal cells. It is possible that TWEAK/Fn14 upregulation in PDR may contribute to PDR progression by promoting the proliferation or fibrosis of retinal cells.

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