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Introduction: Maternal glucocorticoid exposure increases the risk of preterm delivery; however, the association between glucocorticoids and preterm premature rupture of membranes (pPROM)-a direct cause of preterm delivery-has rarely been investigated.Methods: To examine this association, we evaluated the clinical data of patients with systemic lupus erythematosus (SLE). Mechanism analysis was performed in both human amnion-derived mesenchymal cells (as a model for fetal membranes) and the amnion from SLE patients. We characterized the effects of glucocorticoids on the amnion in both models through comprehensive gene expression profiling and by electric cell-substrate impedance sensing in the mesenchymal cells.Results: The average glucocorticoid dose in cases with pPROM (13.3 mg/day, n = 10) was significantly higher than in those without pPROM (8.5 mg/day, n = 65; P < 0.01) among pregnant patients with well-controlled SLE (SLEDAI <4, n = 75); however, we did not observe a statistically significant difference in it between cases with or without chorioamnionitis. Glucocorticoid-treated human amnion mesenchymal cells showed decreased electric resistance between cells, indicating increased permeability. Differentially expressed genes upon glucocorticoid treatment were significantly enriched with cell adhesion-related genes. Among them, ITGA8 was strikingly induced in both the amnion mesenchymal cells and in amnion derived from patients with SLE.Discussion: We observed an association between glucocorticoids and pPROM with non-infectious etiology. Our findings indicate that glucocorticoids increase amnion permeability and modulate cell-adhesion related genes. ITGA8 represents a primary molecule that triggers pPROM through fibrotic remodeling and preventing resealing of the rupture site in fetal amnion. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases that may progress to liver fibrosis or cancer. The present study aimed to investigate the role of microRNA-125b-5p (miR-125b-5p) in NAFLD and to further explore underlying molecular mechanisms. A mouse model of NAFLD was constructed by high cholesterol diet feeding and a cell-model was developed by treating the mouse liver cell line NCTC1469 with palmitic acid. Gain- and loss-of-function experiments were performed to determine the effects of miR-125b-5p, integrin α8 (ITGA8), and the RhoA signaling pathway on liver fibrosis in NAFLD. After the expression levels of miR-125b-5p, ITGA8, and RhoA were determined, liver fibrosis was evaluated in vivo and in vitro. The binding relationship of miR-125b-5p and ITGA8 was then validated. Finally, miR-125b-5p promoter methylation in NAFLD liver tissues and cells was determined. In NAFLD clinical samples, mouse model, and cell-model, miR-125b-5p expression was reduced, while ITGA8 expression was increased. Moreover, miR-125b-5p targeted and downregulated ITGA8, leading to inhibition of the RhoA signaling pathway. In NAFLD liver tissues and cells, the CpG island in the miR-125b-5p promoter was methylated, causing epigenetic silencing of miR-125b-5p. Both miR-125b-5p silencing and ITGA8 overexpression promoted in vitro and in vivo liver fibrosis in NAFLD via activation of the RhoA signaling pathway. Collectively, epigenetic silencing of miR-125b-5p upregulates ITGA8 expression to activate the RhoA signaling pathway, leading to liver fibrosis in NAFLD. • miR-125b-5p is lowly expressed and ITGA8 is highly expressed in NAFLD. • miR-125b-5p promoter is methylated in NAFLD, which epigenetically silenced miR-125b-5p. • miR-125b-5p targets and inhibits ITGA8 expression. • ITGA8 promotes liver fibrosis in NAFLD via the activation of RhoA signaling pathway. • miR-125b-5p inhibits liver fibrosis in NAFLD by inhibiting ITGA8 and RhoA. [ABSTRACT FROM AUTHOR]