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Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-beta-Slug signaling
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Centre for Heart Lung Innovation, St. Paul ’ s Hospital, Vancouver, BC, Canada V6Z 1Y6; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada V6Z 1Y6.
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2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 30, E4320-E4327 p.Article in journal (Refereed) PublishedText
Abstract [en]

Vimentin has been shown to be involved in wound healing, but its functional contribution to this process is poorly understood. Here we describe a previously unrecognized function of vimentin in coordinating fibroblast proliferation and keratinocyte differentiation during wound healing. Loss of vimentin led to a severe deficiency in fibroblast growth, which in turn inhibited the activation of two major initiators of epithelial-mesenchymal transition (EMT), TGF-beta 1 signaling and the Zinc finger transcriptional repressor protein Slug, in vimentin-deficient (VIM-/-) wounds. Correspondingly, VIM-/- wounds exhibited loss of EMT-like keratinocyte activation, limited keratinization, and slow reepithelialization. Furthermore, the fibroblast deficiency abolished collagen accumulation in the VIM-/- wounds. Vimentin reconstitution in VIM-/- fibroblasts restored both their proliferation and TGF-beta 1 production. Similarly, restoring paracrine TGF-beta-Slug-EMT signaling reactivated the transdifferentiation of keratinocytes, reviving their migratory properties, a critical feature for efficient healing. Our results demonstrate that vimentin orchestrates the healing by controlling fibroblast proliferation, TGF-beta 1-Slug signaling, collagen accumulation, and EMT processing, all of which in turn govern the required keratinocyte activation.

Place, publisher, year, edition, pages
2016. Vol. 113, no 30, E4320-E4327 p.
Keyword [en]
vimentin intermediate filaments, wound healing, epithelial-mesenchymal transition, fibroblast proliferation, keratinocyte migration
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-124504DOI: 10.1073/pnas.1519197113ISI: 000380346200011PubMedID: 27466403OAI: oai:DiVA.org:umu-124504DiVA: diva2:954236
Available from: 2016-08-22 Created: 2016-08-15 Last updated: 2016-08-22Bibliographically approved

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Shen, YueNy, Tor
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