Journal article
Interferon regulatory factor 6 regulates keratinocyte migration
Journal of cell science, Vol.127(Pt 13), pp.2840-2848
07/01/2014
DOI: 10.1242/jcs.139246
PMCID: PMC4075356
PMID: 24777480
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.
Details
- Title: Subtitle
- Interferon regulatory factor 6 regulates keratinocyte migration
- Creators
- Leah C Biggs - 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, USARachelle L Naridze - Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USAKris A DeMali - Department of Biochemistry, The University of Iowa, Iowa City, IA 52242, USADaniel F Lusche - Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, IA 52242, USASpencer Kuhl - Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, IA 52242, USADavid R Soll - Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, IA 52242, USABrian C Schutte - Departments of Microbiology and Molecular Genetics and of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USAMartine Dunnwald - 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
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.127(Pt 13), pp.2840-2848
- DOI
- 10.1242/jcs.139246
- PMID
- 24777480
- PMCID
- PMC4075356
- NLM abbreviation
- J Cell Sci
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Publisher
- England
- Grant note
- T35 HL007485 / NHLBI NIH HHS 5T35HL007485-34 / NHLBI NIH HHS AR035313 / NIAMS NIH HHS
- Language
- English
- Date published
- 07/01/2014
- Academic Unit
- Dermatology; Anatomy and Cell Biology; Biology; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984024550202771
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