Several studies have demonstrated that specific proteins called matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are key elements in the remodeling process that occurs in the inner uterus tissue – the endometrium – in healthy women during their menstrual cycle and in women with endometriosis.
In a review study published in the scientific journal Metalloproteinases In Medicine, the authors presented current knowledge on the involvement of MMPs and TIMPs in endometriosis development and progression.
The authors explored the possibility of MMPs as biomarkers for endometriosis diagnosis or even as targets for endometriosis treatment.
Four major features characterize endometriosis: estrogen hormone dependence, progesterone hormone resistance, increased inflammatory response, and deregulation of the immune system. All can be related to the involvement of MMPs and TIMPs in endometriosis.
In this review article the authors explore some aspects of MMPs and TIMPs, such as:
- Their role in endometrium remodeling during the menstrual cycle of healthy women;
- Their differential expression in endometrium and endometriotic lesions in women with endometriosis.
A diagnosis of endometriosis relies on the detection of lesions in the endometrium through surgical procedures. Therefore, it is necessary to find simple and reliable biomarkers for endometriosis detection.
The authors found occasional and unexplained MMPs in the endometrium independent of the disease status or phase of the menstrual cycle. These results discouraged the use of MMPs and TIMPs as diagnostic biomarkers.
However, several studies with experimental animal models of endometriosis have showed that MMPs and TIMPs could be linked to the development of endometriotic lesions.
Drugs such as Metformin (an anti-diabetic drug) or Inderal (an anti-hypertension drug), and others have been associated with inhibiting inflammation and tissue growth in endometriosis animal models, also impacting MMPs and TIMPs activity and expression. These results support the therapeutic approach of targeting these proteins for endometriosis treatment.
However, more studies are needed to gain additional insight into the precise roles of MMPs and TIMPs in endometriosis. These may allow a better understanding of these proteins as potential therapeutic targets for endometriosis development and progression.
Despite some evidence discouraging the use of these proteins as diagnosis biomarkers, the authors pointed out that “MMP contribution to [endometriosis] development and progression is strongly supported by animal models and clearly deserves further investigation, especially in light of the recent advances on new MMP inhibitors.”