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Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways.
J Cell Physiol 2019; 234(11):19964-19976JC

Abstract

In this study, we aimed to investigate the molecular pathway(s) underlying the effect of metformin (MET) on the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Real-time polymerase chain reaction, Western blot analysis, and gelatin zymography were used to assay the effects of MET on MMP and AMPK signaling pathways. In addition, HTOG cells were treated with miR-29b-3p/a scramble control, H19/a negative control, or MET/PBS to explore possible signaling pathway(s) underlying the inhibitory effect of MET on MMP-2/MMP-9. A rat model of polycystic ovary syndrome (PCOS) was also established to validate the molecular mechanism(s) of MET in vivo. The administration of MET suppressed the expression of MMP-9/MMP-2 and mTOR while increasing the expression of Akt and AMPK, indicating that MET reduced the expression of MMPs via the AMPK signaling pathway. Meanwhile, the H19/miR-29b-3p/MMP-9 and H19/miR-29b-3p/MMP-2 signaling pathways were implicated in PCOS, in which the interactions between H19/miR-29b-3p and MMP-9/MMP-2/miR-29b-3p were confirmed. Furthermore, the administration of MET suppressed the expression of H19 while elevating the expression of miR-29b-3p. And the role of MET in PCOS was also confirmed in vivo via examining the activity of H19 and AMPK signaling pathways in cell or serum samples collected from PCOS rats. MET exhibits a therapeutic effect in the treatment of PCOS by reducing the expression of MMPs.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, Central Theater General Hospital of PLA, Wuhan, China.Department of Obstetrics and Gynecology, Central Theater General Hospital of PLA, Wuhan, China.Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30989649

Citation

Chen, Zhilan, et al. "Metformin Treatment Alleviates Polycystic Ovary Syndrome By Decreasing the Expression of MMP-2 and MMP-9 Via H19/miR-29b-3p and AKT/mTOR/autophagy Signaling Pathways." Journal of Cellular Physiology, vol. 234, no. 11, 2019, pp. 19964-19976.
Chen Z, Wei H, Zhao X, et al. Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways. J Cell Physiol. 2019;234(11):19964-19976.
Chen, Z., Wei, H., Zhao, X., Xin, X., Peng, L., Ning, Y., ... Zhang, Q. (2019). Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways. Journal of Cellular Physiology, 234(11), pp. 19964-19976. doi:10.1002/jcp.28594.
Chen Z, et al. Metformin Treatment Alleviates Polycystic Ovary Syndrome By Decreasing the Expression of MMP-2 and MMP-9 Via H19/miR-29b-3p and AKT/mTOR/autophagy Signaling Pathways. J Cell Physiol. 2019;234(11):19964-19976. PubMed PMID: 30989649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP-2 and MMP-9 via H19/miR-29b-3p and AKT/mTOR/autophagy signaling pathways. AU - Chen,Zhilan, AU - Wei,Huafang, AU - Zhao,Xiaoling, AU - Xin,Xin, AU - Peng,Ling, AU - Ning,Yang, AU - Wang,Yapei, AU - Lan,Yanli, AU - Zhang,Qinghua, Y1 - 2019/04/15/ PY - 2018/12/30/received PY - 2019/03/01/revised PY - 2019/03/06/accepted PY - 2019/4/17/pubmed PY - 2019/4/17/medline PY - 2019/4/17/entrez KW - Akt KW - H19 KW - MET KW - MMP-2 KW - MMP-9 KW - PCOS KW - autophagy KW - mTOR KW - miR-29b-3p SP - 19964 EP - 19976 JF - Journal of cellular physiology JO - J. Cell. Physiol. VL - 234 IS - 11 N2 - In this study, we aimed to investigate the molecular pathway(s) underlying the effect of metformin (MET) on the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Real-time polymerase chain reaction, Western blot analysis, and gelatin zymography were used to assay the effects of MET on MMP and AMPK signaling pathways. In addition, HTOG cells were treated with miR-29b-3p/a scramble control, H19/a negative control, or MET/PBS to explore possible signaling pathway(s) underlying the inhibitory effect of MET on MMP-2/MMP-9. A rat model of polycystic ovary syndrome (PCOS) was also established to validate the molecular mechanism(s) of MET in vivo. The administration of MET suppressed the expression of MMP-9/MMP-2 and mTOR while increasing the expression of Akt and AMPK, indicating that MET reduced the expression of MMPs via the AMPK signaling pathway. Meanwhile, the H19/miR-29b-3p/MMP-9 and H19/miR-29b-3p/MMP-2 signaling pathways were implicated in PCOS, in which the interactions between H19/miR-29b-3p and MMP-9/MMP-2/miR-29b-3p were confirmed. Furthermore, the administration of MET suppressed the expression of H19 while elevating the expression of miR-29b-3p. And the role of MET in PCOS was also confirmed in vivo via examining the activity of H19 and AMPK signaling pathways in cell or serum samples collected from PCOS rats. MET exhibits a therapeutic effect in the treatment of PCOS by reducing the expression of MMPs. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/30989649/Metformin_treatment_alleviates_polycystic_ovary_syndrome_by_decreasing_the_expression_of_MMP_2_and_MMP_9_via_H19/miR_29b_3p_and_AKT/mTOR/autophagy_signaling_pathways_ L2 - https://doi.org/10.1002/jcp.28594 DB - PRIME DP - Unbound Medicine ER -