SP1/COL1A2/ZEB1 axis promotes TGF-β2-induced lens epithelial cell proliferation, migration, invasion and EMT process

Lili Zhao; Ping Wang; Lianyi Sun; Weimei Ma; Lei Yu

doi:10.1016/j.exer.2024.110220

SP1/COL1A2/ZEB1 axis promotes TGF-β2-induced lens epithelial cell proliferation, migration, invasion and EMT process

Exp Eye Res. 2024 Dec 20:251:110220. doi: 10.1016/j.exer.2024.110220. Online ahead of print.

Authors

Lili Zhao¹, Ping Wang¹, Lianyi Sun¹, Weimei Ma¹, Lei Yu²

Affiliations

¹ Department of Ophthalmology, Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, Xi'an 710004, China.
² Department of Ophthalmology, Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, Xi'an 710004, China. Electronic address: yulei0904@163.com.

PMID: 39710101
DOI: 10.1016/j.exer.2024.110220

Abstract

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. In this study, we used transforming growth factor beta-2 (TGF-β2)-induced SRA01/04 cells to mimic PCO cell model and explored the functions and underlying mechanisms of specific protein 1 (SP1) in TGF-β2-induced SRA01/04 cell development. MTT assay and EdU assay were carried out to explore the proliferation of SRA01/04 cells. Transwell assay and wound-healing assay were performed to investigate SRA01/04 cell migration and invasion. Chromatin Immunoprecipitation (ChIP) assay, dual-luciferase reporter assay and Co-immunoprecipitation (Co-IP) assay were used to analyze the relations of SP1, COL1A2 and ZEB1. TGF-β2 treatment led to the promotion of SRA01/04 cell proliferation, migration, invasion and EMT process. COL1A2 level was induced by TGF-β2 treatment and COL1A2 knockdown inhibited TGF-β2-induced SRA01/04 cell proliferation, migration, invasion and EMT. SP1 could activate the transcription of COL1A2. SP1 overexpression promoted TGF-β2-induced SRA01/04 cell injury by regulating COL1A2 expression. Moreover, COL1A2 interacted with ZEB1 and COL1A2 knockdown-mediated effects on the proliferation, migration, invasion and EMT of TGF-β2-induced SRA01/04 cells were abrogated by elevating ZEB1. SP1 regulated COL1A2 and then mediated ZEB1 to affect the proliferation, migration, invasion and EMT of TGF-β2-induced SRA01/04 cells.

Keywords: COL1A2; SP1; SRA01/04 cells; TGF-β2; ZEB1.