Akt-mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation.
Although numerous factors are implicated in skin fibrosis, the exact pathophysiology of hypertrophic scarring remains unknown. We recently demonstrated that mechanical force initiates hypertrophic scar formation in a murine model, potentially enhancing cellular survival through Akt. Here, we specifi...
| Publicado en: | Wound Repair & Regeneration Vol. 19; no. 1; pp. 49 - 59 |
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| Autores principales: | , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Jan/Feb2011
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104987366&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104987366 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10671927 DPV jtl: Wound Repair & Regeneration issn: 10671927 maglogo: Y pubinfo: dt: Jan/Feb2011 vid: 19 iid: 1 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104987366 57367209 10.1111/j.1524-475X.2010.00643.x NLM21134033 104987366 ppf: 49 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Akt-mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation. aug: au: Paterno J Vial IN Wong VW Rustad KC Sorkin M Shi Y Bhatt KA Thangarajah H Glotzbach JP Gurtner GC affil: Department of Surgery, School of Medicine, Stanford University, Stanford, California sug: subj: Cicatrix, Hypertrophic Physiopathology Fibroblasts Physiology Signal Transduction Animal Studies Mice Models, Biological Tissue Culture Techniques Immunohistochemistry Unpaired T-Tests Descriptive Statistics Data Analysis Software ab: Although numerous factors are implicated in skin fibrosis, the exact pathophysiology of hypertrophic scarring remains unknown. We recently demonstrated that mechanical force initiates hypertrophic scar formation in a murine model, potentially enhancing cellular survival through Akt. Here, we specifically examined Akt-mediated mechanotransduction in fibroblasts using both strain culture systems and our murine scar model. In vitro, static strain increased fibroblast motility, an effect blocked by wortmannin (a phosphoinositide-3-kinase/Akt inhibitor). We also demonstrated that high-frequency cyclic strain was more effective at inducing Akt phosphorylation than low frequency or static strain. In vivo, Akt phosphorylation was induced by mechanical loading of dermal fibroblasts in both unwounded and wounded murine skin. Mechanically loaded scars also exhibited strong expression of α-smooth muscle actin, a putative marker of pathologic scar formation. In vivo inhibition of Akt increased apoptosis but did not significantly abrogate hypertrophic scar development. These data suggest that although Akt signaling is activated in fibroblasts during mechanical loading of skin, this is not the critical pathway in hypertrophic scar formation. Future studies are needed to fully elucidate the critical mechanotransduction components and pathways which activate skin fibrosis. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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