TY - JOUR
T1 - PAI-1 in granulosa cells is suppressed directly by statin and indirectly by suppressing TGF-β and TNF-α in mononuclear cells by insulin-sensitizing drugs
AU - Yamada-Nomoto, Kaori
AU - Yoshino, Osamu
AU - Akiyama, Ikumi
AU - Iwase, Akira
AU - Ono, Yosuke
AU - Nakamura, Tomoko
AU - Harada, Miyuki
AU - Nakashima, Akitoshi
AU - Shima, Tomoko
AU - Ushijima, Akemi
AU - Osuga, Yutaka
AU - Chang, Russell Jeffrey
AU - Shimasaki, Shunichi
AU - Saito, Shigeru
N1 - Publisher Copyright:
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2017/7
Y1 - 2017/7
N2 - 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 was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-β and TNF-α in peritoneal fluid mononuclear cells (PFMCs) 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-β and TNF-α 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-β and TNF-α mRNA expression in PFMC. Conclusion: 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-β and TNF-α expression in PFMC, respectively.
AB - 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 was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-β and TNF-α in peritoneal fluid mononuclear cells (PFMCs) 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-β and TNF-α 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-β and TNF-α mRNA expression in PFMC. Conclusion: 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-β and TNF-α expression in PFMC, respectively.
KW - PAI-1
KW - granulosa cell
KW - polycystic ovary syndrome
KW - statin
UR - http://www.scopus.com/inward/record.url?scp=85016422592&partnerID=8YFLogxK
U2 - 10.1111/aji.12669
DO - 10.1111/aji.12669
M3 - 学術論文
C2 - 28337819
AN - SCOPUS:85016422592
SN - 1046-7408
VL - 78
JO - American Journal of Reproductive Immunology
JF - American Journal of Reproductive Immunology
IS - 1
M1 - e12669
ER -