Matrix metalloproteinases and their role in endometriosis

The matrix proteinases have many roles in endometriosis pathogenesis and could pose as a potential therapeutic target

Key Points

Highlight

• The use of matrix metalloproteinases as biomarkers in the evaluation of endometriosis might be possible with the help of future studies.
• Their inhibition may also be pivotal in the treatment of endometriosis, however extensive studies are needed to understand the exact mechanism and reduce the side effects.

Importance

• The matrix proteinases (MMPs) are the major constituents of the extracellular matrix and have important roles in tissue remodeling, differentiation, and homeostasis.
• The invasive and angiogenetic properties may play important roles in the establishment of endometriosis.

What's done here

• This is a review study that summarizes the findings in the literature about matrix metalloproteinases and their different properties in endometriosis pathogenesis.
• The probability of their use as biomarkers and therapeutic targets are also discussed and emphasized with the results of different studies on the subject.

Key results

• MMPs are found in both the normal endometrial epithelium and stroma and their levels are affected by the hormones.
• Studies have shown some MMPs such as MMP2 and 9 are expressed more in endometriotic lesions.
• They play parts in endometriosis pathogenesis at cellular levels with the secretion of certain molecules which activate them and at tissue/organ levels with the formation of new blood vessels and the establishment of invasive properties.

Lay Summary

The extracellular matrix harbors important macromolecules such as collagen and glycoproteins which are required for tissue remodeling, differentiation, and homeostasis. The main group of enzymes responsible for these properties is called matrix metalloproteinases (MMPs). It has been proven that MMPs play pivotal roles in tissue remodeling, therefore may contribute to invasion and angiogenesis.

Researchers from China and Singapore have published a review study that compiles the research on MMPs and their significant roles in endometriosis pathogenesis, which was published in the journal “Biomolecules”.

MMPs are endopeptidases that are found in both the endometrial epithelium and stroma. During a normal endometrial cycle, their activation is adjusted by hormone levels. After the endometrium is shed, they play an important role in maintaining tissue remodeling.

At the cellular level, MMPs are involved in the foundation of ectopic endometriotic lesions through cytokines, hormones, and oxidative stress; and they are also thought to have a role in the epithelial-mesenchymal transition which was particularly found to be associated with certain molecules. Studies have shown that certain MMPs, in particular, MMP2 and MMP9 are activated in endometriosis.

At the tissue level, angiogenesis is known to be started by MMPs 1,3,7, and 13 which gives the cell an invasive characteristic. The way MMPs help in the formation of fibrosis through collagen deposition has also been discussed. The impaired immunologic pathways in endometriosis seem to be affected by the regulation of MMPs. The expression of MMP2 and 9 are increased through IL-10 and IFN-γ whereas IL-6 upregulates the expression of MMP9.

The studies that evaluated the most common MMPs in different stages of endometriosis have been mentioned and it is told that they may help in predicting the stage of the disease and to use these MMPs as biomarkers, the clinical studies with larger sample sizes are needed. Some MMP inhibitors have been tried in different clinical settings such as carcinomas and inflammatory conditions but they all showed intolerable side effects. A couple of studies focused on the use of MMP-inhibitors in endometriosis by reducing the MMP-activity however, the exact mechanism of MMPs in endometriosis remains to be unknown therefore it is an area that calls for more exploring. The authors conclude by saying that MMPs are important and critical molecules that could be useful in the treatment of endometriosis but the unanswered questions about their different aspects as therapeutic targets should be assessed in depth.

Research Source: https://pubmed.ncbi.nlm.nih.gov/34827737/