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PAI-1 in granulosa cells is suppressed directly by statin and indirectly by suppressing TGF-? and TNF-? in mononuclear cells by insulin sensitizing drugs #MMPMID28337819
Am J Reprod Immunol 2017[Jul]; 78 (1): ä PMID28337819show ga
Problem: Plasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear. Method of Study: PAI-1 expression in PCOS ovaries were investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-? and TNF-? in peritoneal fluid mononuclear cells (PFMC) were measured with quantitative PCR. Results: Little PAI-1 expression is observed in healthy GCs whereas GCs of PCOS and atretic follicle exhibit distinct expression in vivo. In vitro study using HGrC1 shows that TGF-? and TNF-? increase PAI-1 mRNA and its activity, and both together exhibit a synergistic effect. The expression of PAI-1 mRNA is suppressed by simvastatin. Moreover, insulin sensitizing drugs (metformin, pioglitazone and rosiglitazone) suppress LPS-induced TGF-? and TNF-? mRNA expression in PFMC. Conclusions: Statin and insulin sensitizing drugs may provide a potential therapy for PCOS via down-regulation of PAI-1 expression in GCs and down-regulation of TGF-? and TNF-? expression in PFMC, respectively.