RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice.
Fibroblasts are critical for wound contraction; a pivotal step in wound healing. They produce and modify the extracellular matrix (ECM) required for the proper tissue remodeling. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a key regulator of ECM homeostasis and turnover. How...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4527692?pdf=render |
| _version_ | 1817982809895075840 |
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| author | Jaime Gutiérrez Cristian A Droppelmann Osvaldo Contreras Chiaki Takahashi Enrique Brandan |
| author_facet | Jaime Gutiérrez Cristian A Droppelmann Osvaldo Contreras Chiaki Takahashi Enrique Brandan |
| author_sort | Jaime Gutiérrez |
| collection | DOAJ |
| description | Fibroblasts are critical for wound contraction; a pivotal step in wound healing. They produce and modify the extracellular matrix (ECM) required for the proper tissue remodeling. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a key regulator of ECM homeostasis and turnover. However, its role in wound contraction is presently unknown. Here we describe that Transforming growth factor type β1 (TGF-β1), one of the main pro-fibrotic wound-healing promoting factors, decreases RECK expression in fibroblasts through the Smad and JNK dependent pathways. This TGF-β1 dependent downregulation of RECK occurs with the concomitant increase of β1-integrin, which is required for fibroblasts adhesion and wound contraction through the activation of focal adhesion kinase (FAK). Loss and gain RECK expression experiments performed in different types of fibroblasts indicate that RECK downregulation mediates TGF-β1 dependent β1-integrin expression. Also, reduced levels of RECK potentiate TGF-β1 effects over fibroblasts FAK-dependent contraction, without affecting its cognate signaling. The above results were confirmed on fibroblasts derived from the Reck+/- mice compared to wild type-derived fibroblasts. We observed that Reck+/- mice heal dermal wounds more efficiently than wild type mice. Our results reveal a critical role for RECK in skin wound contraction as a key mediator in the axis: TGF-β1-RECK-β1-integrin. |
| first_indexed | 2024-04-13T23:25:07Z |
| format | Article |
| id | doaj.art-587d7341cb35488882a979b4c55f2bca |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T23:25:07Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-587d7341cb35488882a979b4c55f2bca2022-12-22T02:25:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013500510.1371/journal.pone.0135005RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice.Jaime GutiérrezCristian A DroppelmannOsvaldo ContrerasChiaki TakahashiEnrique BrandanFibroblasts are critical for wound contraction; a pivotal step in wound healing. They produce and modify the extracellular matrix (ECM) required for the proper tissue remodeling. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a key regulator of ECM homeostasis and turnover. However, its role in wound contraction is presently unknown. Here we describe that Transforming growth factor type β1 (TGF-β1), one of the main pro-fibrotic wound-healing promoting factors, decreases RECK expression in fibroblasts through the Smad and JNK dependent pathways. This TGF-β1 dependent downregulation of RECK occurs with the concomitant increase of β1-integrin, which is required for fibroblasts adhesion and wound contraction through the activation of focal adhesion kinase (FAK). Loss and gain RECK expression experiments performed in different types of fibroblasts indicate that RECK downregulation mediates TGF-β1 dependent β1-integrin expression. Also, reduced levels of RECK potentiate TGF-β1 effects over fibroblasts FAK-dependent contraction, without affecting its cognate signaling. The above results were confirmed on fibroblasts derived from the Reck+/- mice compared to wild type-derived fibroblasts. We observed that Reck+/- mice heal dermal wounds more efficiently than wild type mice. Our results reveal a critical role for RECK in skin wound contraction as a key mediator in the axis: TGF-β1-RECK-β1-integrin.http://europepmc.org/articles/PMC4527692?pdf=render |
| spellingShingle | Jaime Gutiérrez Cristian A Droppelmann Osvaldo Contreras Chiaki Takahashi Enrique Brandan RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice. PLoS ONE |
| title | RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice. |
| title_full | RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice. |
| title_fullStr | RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice. |
| title_full_unstemmed | RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice. |
| title_short | RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice. |
| title_sort | reck mediated β1 integrin regulation by tgf β1 is critical for wound contraction in mice |
| url | http://europepmc.org/articles/PMC4527692?pdf=render |
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