ADAMTS12
ADAMTS12: A Matrix Metalloproteinase with Diverse Roles in Tissue Development and Disease
Description
ADAMTS12 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs 12) is a member of the ADAMTS family of metalloproteinase enzymes. It is a multi-domain protein composed of an N-terminal signal peptide, a pro-domain, a catalytic domain, a spacer domain, and a C-terminal thrombospondin-1 (TSP-1) domain. ADAMTS12 is secreted as a pro-enzyme and requires proteolytic cleavage of its pro-domain for activation.
ADAMTS12 is primarily involved in the degradation of proteoglycans, which are components of the extracellular matrix (ECM). Proteoglycans consist of a core protein linked to glycosaminoglycan (GAG) chains. ADAMTS12 specifically cleaves the link between the core protein and the GAG chains, thereby releasing the GAG chains and initiating ECM remodeling.
Associated Diseases
ADAMTS12 has been implicated in the pathogenesis of various diseases, including:
- Osteoarthritis (OA): ADAMTS12 is elevated in OA cartilage and is thought to contribute to cartilage destruction by degrading proteoglycans.
- Cancer: ADAMTS12 is overexpressed in several types of cancer, including breast, lung, and prostate cancer. It promotes cancer cell invasion and metastasis by cleaving ECM components and releasing growth factors.
- Fibrosis: ADAMTS12 is involved in tissue fibrosis by degrading ECM components and promoting the deposition of collagen. It is implicated in fibrotic diseases such as liver cirrhosis and pulmonary fibrosis.
- Cardiovascular disease: ADAMTS12 plays a role in vascular remodeling and plaque stability. Elevated ADAMTS12 levels are associated with increased risk of cardiovascular events, including myocardial infarction and stroke.
Did you Know ?
A study published in Nature Genetics found that a common genetic variant in the ADAMTS12 gene is associated with an increased risk of developing knee OA. Individuals with this variant have a 1.5-fold higher risk of OA compared to individuals without the variant.
