Reproductive biomedicine online · 2025
PAI-1 deficiency inhibits endometrial fibrosis via modulation of the FAK/Src/ERK and AKT signalling pathways.
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Zhao Huishan, Wang Xinrong, Liu Juan, Yu Mingwei, Bao Hongchu
Аннотация
RESEARCH QUESTION: What is the effect and underlying molecular mechanism of plasminogen activator inhibitor 1 (PAI-1) on the progress of endometrial fibrosis in intrauterine adhesions (IUA)?
DESIGN: The expression of PAI-1 was investigated in endometrial tissues from 20 healthy women and 31 individuals with IUA. Quantitative real-time PCR, haematoxylin and eosin staining and immunofluorescence staining were applied to examine the endometrial morphology as well as the expression of mRNA and proteins. An in-vitro model of endometrial fibrosis was constructed by inducing primary human endometrial stromal cells to differentiate into myofibroblasts using transforming growth factor β1 (TGF-β1). The study also examined the alterations in the FAK/Src/ERK and AKT signalling pathways in primary hESC following the knockdown of PAI-1, both before and after TGF-β1 treatment.
RESULTS: There was a dramatically higher expression of PAI-1 mRNA in adhesive endometrial tissues than in normal endometrium from IUA patients (P = 0.0439). A significant difference in PAI-1 concentration was also observed between normal endometrium from healthy women and fibrotic tissues from IUA patients (P = 0.0087). Furthermore, PAI-1 expression was up-regulated following treatment with TGF-β1 in vitro. Moreover, the silencing of PAI-1 inhibited the expression of fibrosis markers (FN1, COL1A1 and α-SMA), revealing that PAI-1 deletion exerted an anti-fibrotic effect. PAI-1 down-regulation also suppressed the activation of the FAK/Src/ERK and AKT signalling pathways as well as the proliferation and migration of TGF-β1-treated primary hESC.
CONCLUSIONS: PAI-1 acts as a regulator of endometrial fibrosis progression via modulation of the FAK/Src/ERK and AKT signalling pathways, offering new insights into the clinical treatment of IUA.
DESIGN: The expression of PAI-1 was investigated in endometrial tissues from 20 healthy women and 31 individuals with IUA. Quantitative real-time PCR, haematoxylin and eosin staining and immunofluorescence staining were applied to examine the endometrial morphology as well as the expression of mRNA and proteins. An in-vitro model of endometrial fibrosis was constructed by inducing primary human endometrial stromal cells to differentiate into myofibroblasts using transforming growth factor β1 (TGF-β1). The study also examined the alterations in the FAK/Src/ERK and AKT signalling pathways in primary hESC following the knockdown of PAI-1, both before and after TGF-β1 treatment.
RESULTS: There was a dramatically higher expression of PAI-1 mRNA in adhesive endometrial tissues than in normal endometrium from IUA patients (P = 0.0439). A significant difference in PAI-1 concentration was also observed between normal endometrium from healthy women and fibrotic tissues from IUA patients (P = 0.0087). Furthermore, PAI-1 expression was up-regulated following treatment with TGF-β1 in vitro. Moreover, the silencing of PAI-1 inhibited the expression of fibrosis markers (FN1, COL1A1 and α-SMA), revealing that PAI-1 deletion exerted an anti-fibrotic effect. PAI-1 down-regulation also suppressed the activation of the FAK/Src/ERK and AKT signalling pathways as well as the proliferation and migration of TGF-β1-treated primary hESC.
CONCLUSIONS: PAI-1 acts as a regulator of endometrial fibrosis progression via modulation of the FAK/Src/ERK and AKT signalling pathways, offering new insights into the clinical treatment of IUA.