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J Cell Sci. 2014 Jul 1;127(Pt 13):2840-8. doi: 10.1242/jcs.139246. Epub 2014 Apr 28.

Interferon regulatory factor 6 regulates keratinocyte migration.

Author information

1
Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA Interdisciplinary Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA.
2
Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA.
3
Department of Biochemistry, The University of Iowa, Iowa City, IA 52242, USA.
4
Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
5
Departments of Microbiology and Molecular Genetics and of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA.
6
Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA Interdisciplinary Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA martine-dunnwald@uiowa.edu.

Abstract

Interferon regulatory factor 6 (Irf6) regulates keratinocyte proliferation and differentiation. In this study, we tested the hypothesis that Irf6 regulates cellular migration and adhesion. Irf6-deficient embryos at 10.5 days post-conception failed to close their wound compared with wild-type embryos. In vitro, Irf6-deficient murine embryonic keratinocytes were delayed in closing a scratch wound. Live imaging of the scratch showed deficient directional migration and reduced speed in cells lacking Irf6. To understand the underlying molecular mechanisms, cell-cell and cell-matrix adhesions were investigated. We show that wild-type and Irf6-deficient keratinocytes adhere similarly to all matrices after 60 min. However, Irf6-deficient keratinocytes were consistently larger and more spread, a phenotype that persisted during the scratch-healing process. Interestingly, Irf6-deficient keratinocytes exhibited an increased network of stress fibers and active RhoA compared with that observed in wild-type keratinocytes. Blocking ROCK, a downstream effector of RhoA, rescued the delay in closing scratch wounds. The expression of Arhgap29, a Rho GTPase-activating protein, was reduced in Irf6-deficient keratinocytes. Taken together, these data suggest that Irf6 functions through the RhoA pathway to regulate cellular migration.

KEYWORDS:

Interferon regulatory factor 6; Keratinocytes; Migration

PMID:
24777480
PMCID:
PMC4075356
DOI:
10.1242/jcs.139246
[Indexed for MEDLINE]
Free PMC Article

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