SB202190 alleviates endometrial fibrosis by modulating the TGF-β/Smad signaling pathway.

The TGF-β/Smad signaling pathway plays important roles in both normal tissue repair and pathological fibrosis of the endometrium. In this study, for in vivo mice experiments, SB202190, a p38 MAPK inhibitor, was administered by subcutaneous injection twice daily for 2 consecutive weeks. For in vitro experiments, 10 ng/mL TGF-β1 was added into human endometrial epithelial cells (HEECs) for stimulation, followed by co-culture with gradient concentrations of SB202190. The Cell Counting Kit-8 (CCK-8) assay was used to assess cell viability, and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining for apoptosis, and a Transwell assay was used to assess cell migration. We introduced SRI-011381 - a Transforming growth factor β (TGF-β)/Smad pathway agonist - along with SB202190 to intervene in HEECs for mechanistic validation. Our results showed that SB202190 treatment significantly increased the number of endometrial glands, reduced collagen deposition, and alleviated inflammation in Intrauterine adhesion (IUA) mouse models. In vitro, SB202190 markedly enhanced HEECs viability, suppressed cell apoptosis, and mitigated inflammatory response, fibrosis progression, and epithelial-mesenchymal transition (EMT). SRI-011381 significantly reversed the effects of SB202190 on fibrosis and EMT in the cell model. These findings suggest that SB202190 alleviates fibrosis and inflammation and inhibits EMT in IUA models by suppressing the TGF-β/Smad signaling pathway.