Role of ATF4 in fibroblast proliferation and apoptosis induced by mechanical trauma through the miR−93-3p/Smad7 axis
Year: 2025
Type: article
Abstract: Stress urinary incontinence (SUI) is a serious disease for females. This study attempts to explore the role of activating transcription factor 4 (ATF4) in mechanical trauma-induced SUI fibroblast cell proliferation and apoptosis, thereby finding a candidate target for SUI treatment. A cell model simulating the condition of SUI was established for the assessment of ATF4, miR-93-3p and Smad7 expression. Cellular biological behaviors were evaluated, and levels of PCNA and Caspase-3 were measured. Mechanically, the enrichment of ATF4 on the miR-93-3p promoter was analyzed. The binding relation between ATF4 and miR-93-3p promoter and between miR-93-3p and Smad7 3'UTR was verified. The mechanism of the ATF4/miR-93-3p/Smad7 pathway in mechanical trauma-induced fibroblast proliferation and apoptosis was validated. ATF4 was upregulated in mechanical trauma-induced fibroblast, and ATF4 silencing promoted mechanical trauma-induced fibroblast proliferation and inhibited apoptosis. ATF4 bound to the miR-93-3p promoter and inhibited miR-93-3p expression. miR-93-3p targeted Smad7 3'UTR to downregulate Smad7 expression. miR-93-3p depletion or Smad7 overexpression could partially neutralize the role of ATF4 knockdown in mechanical trauma-induced fibroblast proliferation and apoptosis. ATF4 promotes apoptosis and inhibits the proliferation of mechanical trauma-induced fibroblasts via the miR-93-3p/Smad7 axis, providing a potential candidate therapeutic target for mechanical trauma-induced SUI.
Source: Stress
Authors: Wei Li, Haitang Chen, Xueyan Hu, Peifan Yang, Mingmin Liu
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,175
OpenAlex ID: W4416784318