Role of ADAM and ADAMTS proteases in pathological tissue remodeling

Wang, Zhaoni; Li, Wanshan; Chen, Shixing; Tang, Xiao Xiao

doi:10.1038/s41420-023-01744-z

Cited by 6 publications

(4 citation statements)

References 63 publications

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Section: Discussionmentioning

confidence: 99%

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

Li,

Williams,

Jackson

et al. 2024

Cells

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Hypertension induces cardiac fibrotic remodelling characterised by the phenotypic switching of cardiac fibroblasts (CFs) and collagen deposition. We tested the hypothesis that Wnt1-inducible signalling pathway protein-1 (WISP-1) promotes CFs’ phenotypic switch, type I collagen synthesis, and in vivo fibrotic remodelling. The treatment of human CFs (HCFs, n = 16) with WISP-1 (500 ng/mL) induced a phenotypic switch (α-smooth muscle actin-positive) and type I procollagen cleavage to an intermediate form of collagen (pC-collagen) in conditioned media after 24h, facilitating collagen maturation. WISP-1-induced collagen processing was mediated by Akt phosphorylation via integrin β1, and disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS-2). WISP-1 wild-type (WISP-1+/+) mice and WISP-1 knockout (WISP-1−/−) mice (n = 5–7) were subcutaneously infused with angiotensin II (AngII, 1000 ng/kg/min) for 28 days. Immunohistochemistry revealed the deletion of WISP-1 attenuated type I collagen deposition in the coronary artery perivascular area compared to WISP-1+/+ mice after a 28-day AngII infusion, and therefore, the deletion of WISP-1 attenuated AngII-induced cardiac fibrosis in vivo. Collectively, our findings demonstrated WISP-1 is a critical mediator in cardiac fibrotic remodelling, by promoting CFs’ activation via the integrin β1-Akt signalling pathway, and induced collagen processing and maturation via ADAMTS-2. Thereby, the modulation of WISP-1 levels could provide potential therapeutic targets in clinical treatment.

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Section: Discussionmentioning

confidence: 99%

“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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

Li,

Williams,

Jackson

et al. 2024

Cells

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“…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 ].…”

Section: Collagen Post-translational Modifications and Their Impact O...mentioning

confidence: 99%

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

Borst,

Meyaard,

Pascoal Ramos

2024

J Transl Med

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Tumors are highly complex and heterogenous ecosystems where malignant cells interact with healthy cells and the surrounding extracellular matrix (ECM). Solid tumors contain large ECM deposits that can constitute up to 60% of the tumor mass. This supports the survival and growth of cancerous cells and plays a critical role in the response to immune therapy. There is untapped potential in targeting the ECM and cell-ECM interactions to improve existing immune therapy and explore novel therapeutic strategies. The most abundant proteins in the ECM are the collagen family. There are 28 different collagen subtypes that can undergo several post-translational modifications (PTMs), which alter both their structure and functionality. Here, we review current knowledge on tumor collagen composition and the consequences of collagen PTMs affecting receptor binding, cell migration and tumor stiffness. Furthermore, we discuss how these alterations impact tumor immune responses and how collagen could be targeted to treat cancer.

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Mohamedi,

Fontanil,

Vega

et al. 2024

IJMS

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Interaction between extracellular matrix (ECM) components plays an important role in the regulation of cellular behavior and hence in tissue function. Consequently, characterization of new interactions within ECM opens the possibility of studying not only the functional but also the pathological consequences derived from those interactions. We have previously described the interaction between fibulin2 and ADAMTS-12 in vitro and the effects of that interaction using cellular models of cancer. Now, we generate a mouse deficient in both ECM components and evaluate functional consequences of their absence using different cancer and inflammation murine models. The main findings indicate that mice deficient in both fibulin2 and ADAMTS12 markedly increase the development of lung tumors following intraperitoneal urethane injections. Moreover, inflammatory phenotype is exacerbated in the lung after LPS treatment as can be inferred from the accumulation of active immune cells in lung parenchyma. Overall, our results suggest that protective effects in cancer or inflammation shown by fibulin2 and ADAMTS12 as interactive partners in vitro are also shown in a more realistic in vivo context.

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Role of ADAM and ADAMTS proteases in pathological tissue remodeling

Cited by 6 publications

References 63 publications

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

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

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

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

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