Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-β–Slug signaling

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Fang Cheng, Yue Shen, Ponnuswamy Mohanasundaram, Michelle Lindström, Johanna Ivaska, Tor Ny, John E. Eriksson
Förläggare: NATL ACAD SCIENCES
Publiceringsår: 2016
Tidskrift: Proceedings of the National Academy of Sciences
Tidskriftsakronym: P NATL ACAD SCI USA
Volym: 113
Nummer: 30
Artikelns första sida, sidnummer: E4320
Artikelns sista sida, sidnummer: E4327
Antal sidor: 8
ISSN: 0027-8424


Abstrakt

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.


Nyckelord

epithelial-mesenchymal transition, fibroblast proliferation, keratinocyte migration, vimentin intermediate filaments

Senast uppdaterad 2019-21-11 vid 05:24