Collagenases mmp-1, mmp-13, and tissue inhibitors timp-1, timp-2: Their role in healthy and complicated pregnancy and potential as preeclampsia biomarkers—a brief review

Abstract

Extracellular matrix (ECM) turnover is characterized by a unique balance between matrix metalloproteinases’ degradation activity and their natural inhibition by collagen specific tissue inhibitors. Human uterine ECM is a complex structure, majorly consisting of proteins as fibrillar collagen types I and III, fibronectin, and laminin. Collagenases are enzymes from the matrix metalloproteinases’ family, which are predominantly involved in fibrillar collagen types I and III degradation. They are mainly represented by matrix metalloproteinase-1,-13 (MMP-1,-13), naturally inhibited by tissue inhibitors (TIMP-1,-2). The collagen structure of the uterus has been shown to be impaired in women with preeclampsia. This is a result of MMPs/TIMPs dysregulation interplay. This review article summarizes the actual available research data in the literature about the role of MMP-1, MMP-13 and TIMP-1, and TIMP-2 in collagen types I and III turnover in healthy and complicated pregnancy. Their potential use as circulating markers for diagnosis, prognosis, and monitoring of the development of preeclampsia is discussed as well.