A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

Abstract

Review 250Introduction A Disintegrin-like and Metalloproteinase with Thrombospondin type-1 motif (ADAMTS) proteinases, which are released outside the cell (soluble), have very critical roles in damage and repair of extracellular matrix (ECM) processes (remodeling) (1). The ADAMTS family, which degrades ECM structural substrates, such as collagen, aggrecan and versican, has 19 family members (2). These enzymes, which are associated with a great deal of vital physiological processes in the ECM, are inhibited by tissue inhibitors of metalloproteinases (TIMPs) (3, 4). Family members of this group are divided into various subgroups according to their tasks in the ECM (Figure 1). ADAMTS1 (METH-1), which was identified for the first time in colon adenocarcinoma, is associated with inflammation (5) and shows anti-angiogenic properties with ADAMTS8 (METH-2) (6, 7). Especially in the physiology of ovulation, there is interest in these proteases. ADAMTS1 also takes important roles in the process of normal growth, fertility, and organogenesis (8). ADAMTS 2, 3, and 14, also known pro-collagen N-proteinases, have important roles in collagen synthesis in the ECM. Various connective tissue diseases are seen in ADAMTS2 deficiency in this group (9). ADAMTS1, -4, -5, -8, -9, -15, -16, and -18 degrade aggrecan, which is the one of the main components of the ECM; so, they are called as aggrecanases (1). ADAMTS1, -4, and -5 degrade brevican and versican, other structural ECM components (10). Versican helps hyaluronan, which is the basic element of the ECM, to stabilize the matrix (11). ADAMTS5 and -6, expressed specifically in the placenta, are thought to be responsible for implantation (12). ADAMTS7 and -12 degrade Cartilage oligomeric matrix protein (COMP), which is an essential glycoprotein in cartilage matrix (13). ADAMTS10 has important roles in the development of tissues of skin and lens. In ADAMTS10 mutations, autosomal recessive Weill-Marchesani syndrome is seen (14). Known as von Willebrand cleaving protease, ADAMTS13 has effects on coagulation and homeostasis. This protease degrades ultralarge VWF multimers that are localized in endothelial surfaces; so, it prevents thrombus formation (9). Thrombotic thrombocytopenic purpura (TTP), a serious problem during pregnancy, occurs in ADAMTS13 deficiency (15). Increased by follicle-stimulating hormone (FSH) and luteinizing hormone (LH), ADAMTS16 degrades a-2 macroglobulin in the ECM (16). ADAMTS17 is involved in estrogen-induced apoptosis in cancer cells (16). ADAMTS9 and -20 are known Playing a key role in the pathophysiology of many diseases, A Disintegrin-like and Metalloproteinase with Thrombospondin type-1 motif (AD-AMTS) proteinases have been attracted more attention in obstetrics and gynecology. First discovered in 1997, this zinc-dependent proteinase family has 19 members today. These enzymes, which are located in the extracellular matrix (ECM), have a lot of very important functions, like matrix formation and resorption, angiogenesis, ovulation, and coagulation. In additio...

Evaluation of second trimester amniotic fluid ADAMTS4, ADAMTS5, interleukin‐6 and tumor necrosis factor‐α levels in patients with gestational diabetes mellitus

“…Previous studies have shown that the ADAMTS family plays an essential role in regulating the menstrual cycle, ovulation, implantation and maintaining pregnancy . Alterations in the extracellular matrix and abnormal placentation are considered leading causes of GDM.…”

“…Previous studies have shown that the ADAMTS family plays an essential role in regulating the menstrual cycle, ovulation, implantation and maintaining pregnancy. 8 Alterations in the extracellular matrix and abnormal placentation are considered leading causes of GDM. Changes in the structure, function and expression of ADAMTS proteins and proteoglycans have been observed in the extracellular matrix of fetal membranes of pregnant women with GDM.…”

Altered Expression of ADAMTSs and HAPLNs in Preeclamptic Placenta

“…Enzymatic activities of these proteases are inhibited by tissue inhibitor of metalloproteinase-3 (TIMP-3) (12). ADAMTSs play a critical role in the remodeling of ECM as well as many other physiological processes, including embryonic development, cell migration, and angiogenesis (13,14). ADAMTS family members have been implicated in the pathologies of many diseases, including cancer, inflammatory conditions, especially arthritic diseases, and atherosclerosis (14).…”

“…ADAMTSs play a critical role in the remodeling of ECM as well as many other physiological processes, including embryonic development, cell migration, and angiogenesis (13,14). ADAMTS family members have been implicated in the pathologies of many diseases, including cancer, inflammatory conditions, especially arthritic diseases, and atherosclerosis (14). A limited number of studies have shown the expression pattern of some ADAMTS subtypes in human placenta and their possible implication in gestational trophoblastic diseases (15,16); however, a more comprehensive study is required to show the expression pattern of all ADAMTS family members in preeclamptic placentas.…”

Effect of insulin on the mRNA expression of procollagen N-proteinases in chondrosarcoma OUMS-27 cells

“…A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteases are a group of secreted proteases that contains 19 members in humans (11). These proteins perform important tasks in the protection of the structure and function of cells in humans, particularly in the turnover and remodeling of the ECM.…”