ArticleThe Journal of biological chemistry2011
Adamts5 deletion blocks murine dermal repair through CD44-mediated aggrecan accumulation and modulation of transforming growth factor β1 (TGFβ1) signaling.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- Histopathologic and immunohistochemical features of capsular tissue around failed Ahmed glaucoma valves.PloS one · 2017Trial
- The ADAMTS family: from extracellular matrix proteases to orchestrators of fibrosis.Cell communication and signaling : CCS · 2026Review
- Longitudinal multimodal characterization of radiation dermatitis in the C57BL/6J mouse model.bioRxiv : the preprint server for biology · 2025Article
- CD44 signaling in skin wound healing and regeneration.Journal of translational medicine · 2025Review
- First Characterization of the Transcriptome of Lung Fibroblasts of SSc Patients and Healthy Donors of African Ancestry.International journal of molecular sciences · 2023Article
- Aggrecan and Hyaluronan: The Infamous Cartilage Polyelectrolytes - Then and Now.Advances in experimental medicine and biology · 2023Article
- ADAM and ADAMTS disintegrin and metalloproteinases as major factors and molecular targets in vascular malfunction and disease.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Isolation and Purification of Versican and Analysis of Versican Proteolysis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cross-Communication Between Knee Osteoarthritis and Fibrosis: Molecular Pathways and Key Molecules.Open access journal of sports medicine · 2022Review
- Extracellular Matrix Deposition and Remodeling after Corneal Alkali Burn in Mice.International journal of molecular sciences · 2021Article
- Connective Tissue Disorders in Domestic Animals.Advances in experimental medicine and biology · 2021Article
- Regulation of ADAMTS Proteases.Frontiers in molecular biosciences · 2021Review
- Interplay between Cell-Surface Receptors and Extracellular Matrix in Skin.Biomolecules · 2020Review
- Article
- ADAMTS-5: A difficult teenager turning 20.International journal of experimental pathology · 2020Review
- In-Vivo Efficacy of Recombinant Human Hyaluronidase (rHuPH20) Injection for Accelerated Healing of Murine Retrocalcaneal Bursitis and Tendinopathy.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- CD44 inhibits α-SMA gene expression via a novel G-actin/MRTF-mediated pathway that intersects with TGFβR/p38MAPK signaling in murine skin fibroblasts.The Journal of biological chemistry · 2019Article
- Small Leucine-Rich Proteoglycans in Skin Wound Healing.Frontiers in pharmacology · 2019Review
- TGF-b1 or hypoxia enhance glucose metabolism and lactate production via HIF1A signaling in tendon cells.Connective tissue research · 2018Article
- Cardiac fibrosis in regenerative medicine: destroy to rebuild.Journal of thoracic disease · 2018Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
ADAMTS5 has been implicated in the degradation of cartilage aggrecan in human osteoarthritis. Here, we describe a novel role for the enzyme in the regulation of TGFβ1 signaling in dermal fibroblasts both in vivo and in vitro. Adamts5(-/-) mice, generated by deletion of exon 2, exhibit impaired contraction and dermal collagen deposition in an excisional wound healing model. This was accompanied by accumulation in the dermal layer of cell aggregates and fibroblastic cells surrounded by a pericellular matrix enriched in full-length aggrecan. Adamts5(-/-) wounds exhibit low expression (relative to wild type) of collagen type I and type III but show a persistently elevated expression of tgfbRII and alk1. Aggrecan deposition and impaired dermal repair in Adamts5(-/-) mice are both dependent on CD44, and Cd44(-/-)/Adamts5(-/-) mice display robust activation of TGFβ receptor II and collagen type III expression and the dermal regeneration seen in WT mice. TGFβ1 treatment of newborn fibroblasts from wild type mice results in Smad2/3 phosphorylation, whereas cells from Adamts5(-/-) mice phosphorylate Smad1/5/8. The altered TGFβ1 response in the Adamts5(-/-) cells is dependent on the presence of aggrecan and expression of CD44, because Cd44(-/-)/Adamts5(-/-) cells respond like WT cells. We propose that ADAMTS5 deficiency in fibrous tissues results in a poor repair response due to the accumulation of aggrecan in the pericellular matrix of fibroblast progenitor cells, which prevents their transition to mature fibroblasts. Thus, the capacity of ADAMTS5 to modulate critical tissue repair signaling events suggests a unique role for this enzyme, which sets it apart from other members of the ADAMTS family of proteases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.