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

Fang Cheng, Yue Shen, Ponnuswamy Mohanasundaram, Michelle Lindström, Johanna Ivaska, Ny Tor, John Eriksson

Tutkimustuotos: LehtiartikkeliArtikkelivertaisarvioitu

149 Sitaatiot (Scopus)

Abstrakti

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.
AlkuperäiskieliEi tiedossa
SivutE4320–E4327
Sivumäärä8
JulkaisuProceedings of the National Academy of Sciences
Vuosikerta113
Numero30
DOI - pysyväislinkit
TilaJulkaistu - 2016
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

Keywords

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

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