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

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.