Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions

• Published in: International journal of molecular sciences Vol. 21; no. 8; p. 2840
• Main Authors: Luddi, Alice, Marrocco, Camilla, Governini, Laura, Semplici, Bianca, Pavone, Valentina, Luisi, Stefano, Petraglia, Felice, Piomboni, Paola
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18-04-2020; MDPI
• Subjects: Adult; Cells, Cultured; Cysts; Cytokines; deep infiltrating endometriosis; Endometriosis; Endometriosis - enzymology; Endometriosis - genetics; Endometriosis - metabolism; Endometrium; Endometrium - enzymology; Endometrium - metabolism; Endometrium - pathology; Epithelial Cells - metabolism; Extracellular matrix; Female; Fluorescent Antibody Technique; Gelatinase A; Gene expression; Gene Expression Profiling; Humans; Immunofluorescence; Inhibitors; Invasiveness; Lesions; Malignancy; Matrix metalloproteinase; Matrix Metalloproteinase 10 - genetics; Matrix Metalloproteinase 10 - metabolism; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 3 - genetics; Matrix Metalloproteinase 3 - metabolism; Matrix metalloproteinases; Menstruation; metalloproteases; Molecular modelling; Molecular weight; ovarian cysts; Pathogenesis; Peritoneum; Proteins; Quantitative analysis; Stromal cells; Stromal Cells - metabolism; Stromelysin 1; Stromelysin 2; Tissue inhibitor of metalloproteinase 1; Tissue inhibitor of metalloproteinase 2; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tissue Inhibitor of Metalloproteinase-2 - genetics; Tissue Inhibitor of Metalloproteinase-2 - metabolism; TNF; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; Uterus; endometriosis; endometrium; metalloproteases; ovarian cysts; TNF; deep infiltrating endometriosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082840

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 (
= 15) and eutopic endometrium (
= 19) in OMA (
= 10) and DIE (
= 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
,
, and
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.