Chen, Kellen and Kwon, Sun Hyung and Henn, Dominic and Kuehlmann, Britta A. and Tevlin, Ruth and Bonham, Clark A. and Griffin, Michelle and Trotsyuk, Artem A. and Borrelli, Mimi R. and Noishiki, Chikage and Padmanabhan, Jagannath and Barrera, Janos A. and Maan, Zeshaan N. and Dohi, Teruyuki and Mays, Chyna J. and Greco, Autumn H. and Sivaraj, Dharshan and Lin, John Q. and Fehlmann, Tobias and Mermin-Bunnell, Alana M. and Mittal, Smiti and Hu, Michael S. and Zamaleeva, Alsu and Keller, Andreas and Rajadas, Jayakumar and Longaker, Michael T. and Januszyk, Michael and Gurtner, Geoffrey C. (2021) Disrupting biological sensors of force promotes tissue regeneration in large organisms. NATURE COMMUNICATIONS, 12 (1): 5256. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)Abstract
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. Humans and other large mammals heal wounds by forming fibrotic scar tissue with diminished function. Here, the authors show that disrupting mechanotransduction through the focal adhesion kinase pathway in large animals accelerates healing, prevents fibrosis, and enhances skin regeneration.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FOCAL ADHESION KINASE; HYPERTROPHIC SCAR; EXPRESSION; FIBROSIS; SKIN; CANCER; TRANSITION; INHIBITOR; REGULATOR; EVOLUTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Zentrum für Plastische-, Hand- und Wiederherstellungschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 09:02 |
| Last Modified: | 13 Sep 2022 09:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47297 |
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