Microfibrillar-associated protein 5 promotes TGF-β1-induced endometrial epithelial fibrosis in intrauterine adhesion†.

Intrauterine adhesion (IUA) is an adhesion of the uterine cavity or cervical canal resulting from damage to the basal layer of the endometrium， usually accompanied by fibrosis of the endometrium. This study analyzed endometrial samples from three IUA patients and three healthy control participants and screened for differentially expressed genes (DEGs) using RNA-seq and bioinformatics techniques. A total of 2402 DEGs were identified in endometrial tissues compared to normal endometrial tissues, among which microfibrillar-associated protein 5 (MFAP5) was upregulated in IUA tissues (log2FoldChange = 3.81, P = 1.98E-08). Meanwhile, clinical tissue specimens revealed remarkably up-regulated MFAP5 expression in endometrial tissues of IUA patients, accompanied by increases in the fibrosis markers collagen type I A 1 and α-smooth muscle actin. A mouse model of IUA was constructed by mechanical curettage. Histopathology revealed that MFAP5 downregulation attenuated IUA model-induced reduction in endometrial gland number and collagen deposition. Furthermore, MFAP5 knockdown alleviated the increase in embryo uptake ratio and the decrease in embryo and placental weight in IUA model. In vitro, the expression of fibrosis indicators was upregulated in Ishikawa cells treated with 5 ng/mL transforming growth factor-β1 (TGF-β1), while MFAP5 siRNA reduced levels of the endometrial fibrosis markers. RNA-seq analysis was performed on normal-treated and MFAP5 knockdown-treated TGF-β1-induced cell lines. Enrichment analysis revealed that the MFAP5 siRNA may be involved in microfibril formation, collagen deposition, and the TGF-β pathway. These results further confirm the potential role of MFAP5 in promoting endometrial fibrosis, which provides new insight for the clinical treatment of IUA.