Abstract
Novel Regulators of Epithelial Migration and Differentiation
The FASEB journal, Vol.32(S1), pp.86.1-86.1
04/2018
DOI: 10.1096/fasebj.2018.32.1_supplement.86.1
Abstract
Epithelial migration and differentiation are key cellular processes required for wound closure. We recently identified Interferon Regulatory Factor 6 (IRF6) as a transcription factor that regulates both of these processes. We previously demonstrated that Irf6‐deficient embryos and Irf6‐deficient keratinocytes displayed impaired wound healing and cellular migration. Furthermore, individuals with IRF6 mutations (van der Woude syndrome, the most common form of syndromic orofacial cleft) exhibited increased likelihood of wound healing complications following surgical repair. Therefore, we hypothesized that altered expression of Irf6 and its downstream effectors would lead to impaired wound healing in adults. Using murine models with different Irf6 levels, we showed that reduced levels of Irf6 are more detrimental in early stages of wound healing (day 4) and increased levels are more detrimental in late stages of wound healing (day 7). Furthermore, keratinocytes from syndromic orofacial cleft patients were slower at closing an in vitro scratch compared to non‐syndromic keratinocytes. One of the downstream targets of Irf6 is Arhgap29 (Rho GTPase Activating Protein 29). Arhgap29 is decreased in the absence of Irf6, and could mediate the Irf6‐dependent migration. We are currently testing the role of Arhgap29 in vivo using a novel Arhgap29 allele containing a genetic variant identified in a patient with cleft lip and palate. Together, these results demonstrate that the positive and negative perturbation of the levels of Irf6 lead to defects throughout the entire period of wound healing. Ultimately, these data suggest the existence of a critical therapeutic window for IRF6 that should be considered in designing new clinical treatments for wound healing.
Support or Funding Information
NIH/MIAMS AR067739
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
Details
- Title: Subtitle
- Novel Regulators of Epithelial Migration and Differentiation
- Creators
- Martine Dunnwald - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.32(S1), pp.86.1-86.1
- DOI
- 10.1096/fasebj.2018.32.1_supplement.86.1
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Publisher
- The Federation of American Societies for Experimental Biology
- Number of pages
- 1
- Grant note
- NIH/MIAMS (AR067739)
- Language
- English
- Date published
- 04/2018
- Academic Unit
- Anatomy and Cell Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984288802602771
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