Interferon regulatory factor 6 regulates keratinocyte migration.

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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Biggs LC,Naridze RL,DeMali KA,Lusche DF,Kuhl S,Soll DR,Schutte BC,Dunnwald M

doi

10.1242/jcs.139246

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

2840-8

issue

Pt 13

eissn

0021-9533

issn

1477-9137

pii

jcs.139246

journal_volume

127

pub_type

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