advertisement
Abstract #127329 Published in IGR 25-3
Transcription factor SP1 drives TGF-β1-induced transformation of human tenon's capsule fibroblasts by transcription activation-mediated SNAI2 upregulation
Chen Y; Li C; Bai Z; Yang H; Wang Q; Zhang YInternational Ophthalmology 2025; 45: 243
BACKGROUND: Glaucoma is an irreversible blinding disease worldwide with complex pathogenesis. Previous studies have indicated that Specificity protein 1 (SP1) plays a critical role in diverse diseases, including glaucoma. This study is designed to explore the role and underlying mechanism of SP1 in the development of glaucoma. METHODS: SP1 and Snail Family Transcriptional Repressor 2 (SNAI2) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). SP1, SNAI2, Fibronectin, α-SMA, E-cadherin, LC3BI, LC3BII, and p62 protein levels were assessed using western blot assay. Binding between SP1 and SNAI2 promoter was predicted by JASPAR and validated using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. Cell viability, migration, and invasion were measured using Cell Counting Kit-8 (CCK-8), transwell, and wound healing assays. RESULTS: SP1 and SNAI2 were highly expressed in glaucoma patients and transforming growth factor beta-1 (TGF-β1)-treated human Tenon's capsule fibroblast cells (HTFs). At the molecular level, SP1 was a transcription factor of SNAI2 and increased the transcriptional activity of SNAI2 by binding to its promoter region. SP1 knockdown could relieve TGF-β1-induced HTF viability, migration, invasion, extracellular matrix (ECM) deposition, and autophagy. CONCLUSION: SP1-activated SNAI2 transcription promotes TGF-β1-triggered HTF viability, migration, invasion, ECM deposition, and autophagy, which provides a promising therapeutic target for glaucoma treatment.
Department of Ophthalmology, Pu'er People's Hospital, Pu'er, 665000, Yunnan, China.
Full article