Universität zu Köln

Volksdorf, Thomas, Heilmann, Janina, Eming, Sabine A., Schawjinski, Kathrin, Zorn-Kruppa, Michaela, Ueck, Christopher, Vidal-y-Sy, Sabine, Windhorst, Sabine, Juecker, Manfred, Moll, Ingrid and Brandner, Johanna M. (2017). Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing. Am. J. Pathol., 187 (6). S. 1301 - 1313. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

Tight junction (TJ) proteins are known to be involved in proliferation and differentiation. These processes are essential for normal skin wound healing. Here, we investigated the TJ proteins claudin-1 and occludin in ex vivo skin wound healing models and tissue samples of acute and chronic human wounds and observed major differences in localization/expression of these proteins, with chronic wounds often showing a loss of the proteins at the wound margins and/or in the regenerating epidermis. Knockdown experiments in primary human keratinocytes showed that decreased claudin-1 expression resulted in significantly impaired scratch wound healing, with delayed migration and reduced proliferation. Activation of AKT pathway was significantly attenuated after claudin-1 knockdown, and protein levels of extracellular signal-related kinase 1/2 were reduced. For occludin, down-regulation had no impact on wound healing in normal scratch assays, but after subjecting the cells to mechanical stress, which is normally present in wounds, wound healing was impaired. For both proteins we show that most of these actions are independent from the formation of barrier-forming TJ structures, thus demonstrating nonbarrier-related functions of TJ proteins in the skin. However, for claudin-1 effects on scratch wound healing were more pronounced when TJs could form. Together, our findings provide evidence for a role of claudin-1 and occludin in epidermal regeneration with potential clinical importance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Volksdorf, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilmann, Janina UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schawjinski, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Zorn-Kruppa, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Ueck, Christopher UNSPECIFIED UNSPECIFIED UNSPECIFIED Vidal-y-Sy, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Windhorst, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Juecker, Manfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Moll, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandner, Johanna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-229245
DOI:	10.1016/j.ajpath.2017.02.006
Journal or Publication Title:	Am. J. Pathol.
Volume:	187
Number:	6
Page Range:	S. 1301 - 1313
Date:	2017
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1525-2191
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLLECTIVE CELL-MIGRATION; SIGNALING PATHWAYS; BARRIER FUNCTION; IN-VITRO; CLAUDIN-1-DEFICIENT MICE; EPIDERMAL-KERATINOCYTES; CANCER-CELLS; REPAIR; PROLIFERATION; DIFFERENTIATION Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22924