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Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis

Mioduchowska Anna Szóstek Słowińska Mariola Pacewicz Joanna Skarzynski Dariusz J. Okuda Kiyoshi 帯広畜産大学

2020.03.04

概要

Equine endometrial fibrosis (endometrosis) is described as a degenerative chronic condition in the uterus. Its characteristic feature is excessive deposition of extracellular matrix (ECM) components around the endometrial glands and stroma. Although matrix metallopeptidases (MMPs) that mediate ECM turnover are important factors in the process of fibrosis, knowledge of their expression and regulation in endometrosis is limited. In other species, one of the important regulators of MMPs and tissue inhibitors of MMPs (TIMPs) is transforming growth factor (TGF)-β1. The goal of this study was to determine (i) endometrial expression of MMPs and TIMPs during endometrosis and (ii) the effect of TGF-β1 on expression of MMPs and TIMPs in equine endometrial fibroblasts and epithelial cells. In the follicular phase of the estrous cycle, MMP-1, -2, -9, and TIMP concentrations were higher during endometrosis than in healthy endometrium (P < 0.05). In the midluteal phase, MMP-3 concentration was lower in severe endometrosis compared to healthy endometrium (P < 0.05). In fibroblasts, TGF-β1 upregulated MMP-1, -9, -13, and TIMP1, but downregulated MMP-3 secretion (P < 0.05). In epithelial cells, TGF-β1 upregulated MMP-1, -9, -13, and TIMP secretion (P < 0.05). Endometrial expression of MMPs and TIMPs is altered during endometrosis. TGF-β1 is a regulator of endometrial ECM remodeling via its effect on MMPs and TIMPs in equine endometrial fibroblasts and epithelial cells.

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Acknowledgements

The authors would like to thank to dr Beenu Jalali for her comments on the manuscript and Agnieszka Bacławska

for her technical assistance. Funded by KNOW (Leading National Research Centre) Scientific Consortium

“Healthy Animal - Safe Food”, decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015.

A.Sz-M was supported by Post-Doctoral Fellowship Program of the Japan Society for the Promotion of Science

(JSPS) (P14802).

Author contributions

A.S.z.-M. - developed the study concept, carried out experiments, analyzed and interpreted the results, and wrote

the manuscript. D.J.S., K.O. - contributed to the study concept and revised the manuscript; J.P. - participated in

isolation and culture of epithelial cells; M.S. - carried out zymography and analyzed the results.

Competing interests

The authors declare no competing interests.

Additional information

Supplementary information is available for this paper at https://doi.org/10.1038/s41598-020-58109-0.

Correspondence and requests for materials should be addressed to A.S.-M.

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