GLCCI1 alleviates GRP78-initiated endoplasmic reticulum stress-induced apoptosis of retinal ganglion cells in diabetic retinopathy by upregulating and interacting with HSP90AB1.

Autor: Liu J; School of Basic Medical Sciences, Guangxi Medical University, Nanning City, People's Republic of China.; School of Basic and Forensic Medical Sciences, North Sichuan Medical College, Nanchong City, People's Republic of China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China., Yu H; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China., Yu S; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China., Liu M; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China.; School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou City, People's Republic of China., Chen X; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China.; School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou City, People's Republic of China., Wang Y; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China.; School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou City, People's Republic of China., Li J; Department of Educational Affairs, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou City, People's Republic of China., Shi C; School of Basic Medicine, Jining Medical University, Jining City, People's Republic of China., Liu W; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China.; School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou City, People's Republic of China., Zuo Z; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China. zuozhongfu@jzmu.edu.cn.; School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou City, People's Republic of China. zuozhongfu@jzmu.edu.cn., Liu X; School of Basic Medical Sciences, Guangxi Medical University, Nanning City, People's Republic of China. liuxuezheng@jzmu.edu.cn.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou City, Liaoning Province, People's Republic of China. liuxuezheng@jzmu.edu.cn.; School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou City, People's Republic of China. liuxuezheng@jzmu.edu.cn.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 04; Vol. 14 (1), pp. 26665. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1038/s41598-024-75874-4
Abstrakt: Retinal ganglion cells (RGCs) are among the first neurons to undergo apoptosis in diabetic retinopathy (DR), with their relationship to endoplasmic reticulum stress (ERS)-induced apoptosis still unclear. While glucocorticoid-induced transcript 1 (GLCCI1) has been shown to inhibit apoptosis, its role in ERS-induced apoptosis and its mechanisms in DR remain unclarified. Our findings indicated that GLCCI1 is predominantly localized in the ganglion cell layer and is downregulated in DR. GLCCI1 overexpression mitigated the apoptosis of RGCs and the swelling of endoplasmic reticulum and mitochondria under hyperglycemia, and downregulated ERS-induced apoptosis related markers (GRP78, CHOP and cleaved CASP3), whereas GLCCI1 knockdown has the opposite effect. In vivo, GLCCI1 overexpression not only prevents structural lesions but also protects against microvascular dysfunctions in the retinas of DR mice. We found that GLCCI1 directly interacts with HSP90AB1, which in turn interacts with GRP78. Additionally, GLCCI1 is an upstream regulator of HSP90AB1, which regulates GRP78. Thus, the impact of GLCCI1 on the ERS-induced apoptosis is mainly through the regulation of HSP90AB1, and subsequently inhibiting GRP78-initiated ERS-induced apoptosis. These findings offer a promising avenue for further treatment of DR.
(© 2024. The Author(s).)
Databáze: MEDLINE
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