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Disrupting biological sensors of force promotes tissue regeneration in large organisms.
Chen, Kellen; Kwon, Sun Hyung; Henn, Dominic; Kuehlmann, Britta A; Tevlin, Ruth; Bonham, Clark A; Griffin, Michelle; Trotsyuk, Artem A; Borrelli, Mimi R; Noishiki, Chikage; Padmanabhan, Jagannath; Barrera, Janos A; Maan, Zeshaan N; Dohi, Teruyuki; Mays, Chyna J; Greco, Autumn H; Sivaraj, Dharshan; Lin, John Q; Fehlmann, Tobias; Mermin-Bunnell, Alana M; Mittal, Smiti; Hu, Michael S; Zamaleeva, Alsu I; Keller, Andreas; Rajadas, Jayakumar; Longaker, Michael T; Januszyk, Michael; Gurtner, Geoffrey C.
Afiliación
  • Chen K; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Kwon SH; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Henn D; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Kuehlmann BA; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Tevlin R; University Center for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Regensburg and Caritas Hospital St. Josef, Franz-Josef-Strauss-Allee 11, Regensburg, Germany.
  • Bonham CA; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Griffin M; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Trotsyuk AA; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Borrelli MR; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Noishiki C; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Padmanabhan J; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Barrera JA; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Maan ZN; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Dohi T; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Mays CJ; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Greco AH; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Sivaraj D; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Lin JQ; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Fehlmann T; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Mermin-Bunnell AM; Clinical Bioinformatics, Saarland University, Saarbruecken, Germany.
  • Mittal S; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Hu MS; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Zamaleeva AI; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Keller A; Biomaterials and Advanced Drug Delivery Laboratory, Stanford University, Stanford, CA, USA.
  • Rajadas J; Clinical Bioinformatics, Saarland University, Saarbruecken, Germany.
  • Longaker MT; Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA.
  • Januszyk M; Biomaterials and Advanced Drug Delivery Laboratory, Stanford University, Stanford, CA, USA.
  • Gurtner GC; Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Nat Commun ; 12(1): 5256, 2021 09 06.
Article en En | MEDLINE | ID: mdl-34489407
Tissue repair and healing remain among the most complicated processes that occur during postnatal life. Humans and other large organisms heal by forming fibrotic scar tissue with diminished function, while smaller organisms respond with scarless tissue regeneration and functional restoration. Well-established scaling principles reveal that organism size exponentially correlates with peak tissue forces during movement, and evolutionary responses have compensated by strengthening organ-level mechanical properties. How these adaptations may affect tissue injury has not been previously examined in large animals and humans. Here, we show that blocking mechanotransduction signaling through the focal adhesion kinase pathway in large animals significantly accelerates wound healing and enhances regeneration of skin with secondary structures such as hair follicles. In human cells, we demonstrate that mechanical forces shift fibroblasts toward pro-fibrotic phenotypes driven by ERK-YAP activation, leading to myofibroblast differentiation and excessive collagen production. Disruption of mechanical signaling specifically abrogates these responses and instead promotes regenerative fibroblast clusters characterized by AKT-EGR1.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Sulfonamidas / Cicatrización de Heridas / Mecanotransducción Celular / Indoles Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Sulfonamidas / Cicatrización de Heridas / Mecanotransducción Celular / Indoles Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido