Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions
by
Alice Luddi 1,†, Camilla Marrocco 1,†, Laura Governini 1, Bianca Semplici 1, Valentina Pavone 1, Stefano Luisi 1, Felice Petraglia 2 and Paola Piomboni 1,*
Alice Luddi 1,†, Camilla Marrocco 1,†, Laura Governini 1, Bianca Semplici 1, Valentina Pavone 1, Stefano Luisi 1, Felice Petraglia 2 and Paola Piomboni 1,*
1
Department of Molecular and Developmental Medicine, Siena University, 53100 Siena, Italy
2
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(8), 2840; https://doi.org/10.3390/ijms21082840
Received: 11 March 2020 / Revised: 15 April 2020 / Accepted: 16 April 2020 / Published: 18 April 2020
(This article belongs to the Special Issue Molecular Pathophysiology of Uterine and Ovarian Diseases and Dysfunction)
Endometriosis is a condition defined as presence of endometrium outside of the uterine cavity. These endometrial cells are able to attach and invade the peritoneum or ovary, thus forming respectively the deep infiltrating endometriosis (DIE) and the ovarian endometrioma (OMA), the ectopic lesions feature of this pathology. Endometriotic cells display high invasiveness and share some features of malignancy with cancer cells. Indeed, the tissue remodeling underlining lesion formation is achieved by matrix metalloproteinases (MMPs) and their inhibitors. Therefore, these molecules are believed to play a key role in development and pathogenesis of endometriosis. This study investigated the molecular profile of metalloproteinases and their inhibitors in healthy (n = 15) and eutopic endometrium (n = 19) in OMA (n = 10) and DIE (n = 9); moreover, we firstly validated the most reliable housekeeping genes allowing accurate gene expression analysis in these tissues. Gene expression, Western blot, and immunofluorescence analysis of MMP2, MMP3, and MMP10 and their tissue inhibitors TIMP1 and TIMP2 demonstrated that these enzymes are finely tuned in these tissues. In OMA lesions, all the investigated MMPs and their inhibitors were significantly increased, while DIE expressed high levels of MMP3. Finally, in vitro TNFα treatment induced a significant upregulation of MMP3, MMP10, and TIMP2 in both healthy and eutopic endometrial stromal cells. This study, shedding light on MMP and TIMP expression in endometriosis, confirms that these molecules are altered both in eutopic endometrium and endometriotic lesions. Although further studies are needed, these data may help in understanding the molecular mechanisms involved in the extracellular matrix remodeling, a crucial process for the endometrial physiology.
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Keywords:
endometriosis; ovarian cysts; deep infiltrating endometriosis; metalloproteases; TNF; endometrium
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MDPI and ACS Style
Luddi, A.; Marrocco, C.; Governini, L.; Semplici, B.; Pavone, V.; Luisi, S.; Petraglia, F.; Piomboni, P. Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions. Int. J. Mol. Sci. 2020, 21, 2840.
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