Role of ADAM and ADAMTS proteases in pathological tissue remodeling

Abstract

Pathological tissue remodeling is closely associated with the occurrence and aggravation of various diseases. A Disintegrin And Metalloproteinases (ADAM), as well as A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS), belong to zinc-dependent metalloproteinase superfamily, are involved in a range of pathological states, including cancer metastasis, inflammatory disorders, respiratory diseases and cardiovascular diseases. Mounting studies suggest that ADAM and ADAMTS proteases contribute to the development of tissue remodeling in various diseases, mainly through the regulation of cell proliferation, apoptosis, migration and extracellular matrix remodeling. This review focuses on the roles of ADAM and ADAMTS proteinases in diseases with pathological tissue remodeling, with particular emphasis on the molecular mechanisms through which ADAM and ADAMTS proteins mediate tissue remodeling. Some of these reported proteinases have defined protective or contributing roles in indicated diseases, while their underlying regulation is obscure. Future studies are warranted to better understand the catalytic and non-catalytic functions of ADAM and ADAMTS proteins, as well as to evaluate the efficacy of targeting these proteases in pathological tissue remodeling.

WISP-1 Regulates Cardiac Fibrosis by Promoting Cardiac Fibroblasts’ Activation and Collagen Processing

“…To date, 19 zinc-mediated ADAMTS metalloproteinases have been identified in humans [ 48 , 49 ]. Among them, ADAMTS-2, -3, and -14 are primarily involved in fibril-forming collagen processing [ 17 , 48 , 49 ].…”

“…To date, 19 zinc-mediated ADAMTS metalloproteinases have been identified in humans [ 48 , 49 ]. Among them, ADAMTS-2, -3, and -14 are primarily involved in fibril-forming collagen processing [ 17 , 48 , 49 ]. ADAMTS-3, which is predominantly expressed in cartilage, primarily cleaves type II procollagen [ 50 ].…”

Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy

“…The ECM undergoes constant remodeling involving collagen cleavage by proteases such as matrix metalloproteases (MMPs), a disintegrin and metalloproteinases (ADAMs) and ADAM with thrombospondin motifs (ADAMTs) [ 120 , 121 ]. These enzymes directly influence the biological characteristics and functions of collagen by uncovering cryptic sites, releasing collagen-bound growth factors and degrading collagen [ 122 ].…”

Lung Inflammatory Phenotype in Mice Deficient in Fibulin-2 and ADAMTS-12

“…The ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin domains) comprise a family of 19 extracellular human metalloproteinases containing a variable number of type-1 thrombospondin (TSP-1) domains at the carboxy-end region that provides specific binding properties to ECM molecules that makes them unique [25]. ADAMTSs are associated with a series of processes such as cell proliferation, adhesion, migration, angiogenesis and maturation of stroma cells, which would finally have an important impact on tumor biology [26].…”