| Added by | tchardes |
|---|---|
| Group name | EquipeELC |
| Item Type | Journal Article |
| Title | BMP-1 disrupts cell adhesion and enhances TGF-? activation through cleavage of the matricellular protein thrombospondin-1 |
| Creator | Anastasi et al. |
| Author | Cyril Anastasi |
| Author | Patricia Rousselle |
| Author | Maya Talantikite |
| Author | Agnès Tessier |
| Author | Caroline Cluzel |
| Author | Alice Bachmann |
| Author | Natacha Mariano |
| Author | Mélissa Dussoyer |
| Author | Lindsay B. Alcaraz |
| Author | Laëtitia Fortin |
| Author | Alexandre Aubert |
| Author | Frédéric Delolme |
| Author | Naïma El Kholti |
| Author | Jean Armengaud |
| Author | Pierre Fournié |
| Author | Céline Auxenfans |
| Author | Ulrich Valcourt |
| Author | Sandrine Vadon-Le Goff |
| Author | Catherine Moali |
| Abstract | Bone morphogenetic protein 1 (BMP-1) is an important metalloproteinase that synchronizes growth factor activation with extracellular matrix assembly during morphogenesis and tissue repair. The mechanisms by which BMP-1 exerts these effects are highly context dependent. Because BMP-1 overexpression induces marked phenotypic changes in two human cell lines (HT1080 and 293-EBNA cells), we investigated how BMP-1 simultaneously affects cell-matrix interactions and growth factor activity in these cells. Increasing BMP-1 led to a loss of cell adhesion that depended on the matricellular glycoprotein thrombospondin-1 (TSP-1). BMP-1 cleaved TSP-1 between the VWFC/procollagen-like domain and the type 1 repeats that mediate several key TSP-1 functions. This cleavage induced the release of TSP-1 C-terminal domains from the extracellular matrix and abolished its previously described multisite cooperative interactions with heparan sulfate proteoglycans and CD36 on HT1080 cells. In addition, BMP-1-dependent proteolysis potentiated the TSP-1-mediated activation of latent transforming growth factor-? (TGF-?), leading to increased signaling through the canonical SMAD pathway. In primary human corneal stromal cells (keratocytes), endogenous BMP-1 cleaved TSP-1, and the addition of exogenous BMP-1 enhanced cleavage, but this had no substantial effect on cell adhesion. Instead, processed TSP-1 promoted the differentiation of keratocytes into myofibroblasts and stimulated production of the myofibroblast marker ?-SMA, consistent with the presence of processed TSP-1 in human corneal scars. Our results indicate that BMP-1 can both trigger the disruption of cell adhesion and stimulate TGF-? signaling in TSP-1-rich microenvironments, which has important potential consequences for wound healing and tumor progression. |
| Publication | Science Signaling |
| Volume | 13 |
| Issue | 639 |
| Date | 2020-07-07 |
| Journal Abbr | Sci Signal |
| Language | eng |
| DOI | 10.1126/scisignal.aba3880 |
| ISSN | 1937-9145 |
| Library Catalog | PubMed |
| Extra | PMID: 32636307 |
| Tags | original |
| Date Added | 2021/03/19 - 17:01:14 |
| Date Modified | 2021/03/19 - 17:14:29 |
| Notes and Attachments | PubMed entry (Attachment) Version soumise (Attachment) |
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