TNF-α released from retinal Müller cells aggravates retinal pigment epithelium cell apoptosis by upregulating mitophagy during diabetic retinopathy
| Autor: | Jie Shuai, Guoping Cao, Jiayi Gu, Lili Dong, Lele Li, Yuping Dou, Zhaoxian Qiu, Yu Liu, Ningxin Pan, Aimin Sang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine p38 mitogen-activated protein kinases Ependymoglial Cells Cell Biophysics Apoptosis Retinal Pigment Epithelium Diet High-Fat Biochemistry Diabetes Mellitus Experimental Mice 03 medical and health sciences 0302 clinical medicine Blood-Retinal Barrier Mitophagy medicine Animals Humans Epidermal growth factor receptor Protein kinase A Molecular Biology Cell damage Cells Cultured Diabetic Retinopathy Retinal pigment epithelium biology Tumor Necrosis Factor-alpha Chemistry Cell Biology medicine.disease Coculture Techniques Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research biology.protein sense organs |
| Zdroj: | Biochemical and Biophysical Research Communications. 561:143-150 |
| ISSN: | 0006-291X |
| Popis: | Retinal pigment epithelium (RPE) cell damage, including mitophagy-associated cell apoptosis, accelerates the pathogenesis of diabetic retinopathy (DR), a common complication of diabetes that causes blindness. Müller cells interact with RPE cells via pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α). Herein, we investigated the role of the RPE cell epidermal growth factor receptor (EGFR)/p38 mitogen-activated protein kinase (p38)/nuclear factor kappa B (NF-κB) pathway in Müller cell-derived TNF-α-induced mitophagy-associated apoptosis during DR. Our results showed that TNF-α released from Müller cells activated the EGFR/p38/NF-κB/p62 pathway to increase mitophagy and apoptosis in RPE cells under high glucose (HG) conditions. Additionally, blockade of the TNF-α/EGFR axis alleviates blood-retina barrier breakdown in diabetic mice. Our data further illustrate the effects of the Müller cell inflammatory response on RPE cell survival, implying potential molecular targets for DR treatment. |
| Databáze: | OpenAIRE |
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