Epiplakin accelerates the lateral organization of keratin filaments during wound healing.

Abstract

BACKGROUND:

Epiplakin (EPPK) belongs to the plakin family of cytolinker proteins and, resembling other members of the plakin family such as BPAG1 (an autoantigen of bullous pemphigoid) and plectin, EPPK has plakin repeat domains (PRDs) that bind to intermediate filaments. Elimination of EPPK by gene targeting in mice resulted in the acceleration of keratinocyte migration during wound healing. EPPK is expressed in proliferating keratinocytes at wound edges and, in view of its putative function in binding to keratin, we postulated that the keratin network in EPPK-null (EPPK(-/-)) mice might be disrupted during wound healing.

OBJECTIVE:

To examine this hypothesis and to determine the precise localization of EPPK in relation to keratin filaments, we compared the non-wounded and wounded epidermis of wild-type and EPPK(-/-) mice.

METHODS:

Non-wounded epidermis and wounded epidermis from wild-type and EPPK(-/-) mice were examined by immunofluorescence staining and electron microscopy before and after double immunostaining.

RESULTS:

EPPK was colocalized with keratin 17 (K17) more extensively than with other keratins examined in wounded epidermis. The expression of K5, K10, K6, and K17 was the same in EPPK(-/-) mice after wounding as in normal mice, but diameters of keratin filaments were reduced in EPPK(-/-) keratinocytes. Electron microscopy after immunostaining revealed that EPPK colocalized with K5, K10 and K6 after wounding in wild-type mice.

CONCLUSION:

Our data indicate that EPPK accelerates keratin bundling in proliferating keratinocytes during wound healing and suggest that EPPK might contribute to reinforcement of keratin networks under mechanical stress.

• Authors: Kazushi Ishikawa, Hideaki Sumiyoshi, Noritaka Matsuo, Naoko Takeo, Mizuki Goto, Osamu Okamoto, Shuji Tatsukawa, Hirokazu Kitamura, Yoshihisa Fujikura, Hidekatsu Yoshioka, Sakuhei Fujiwara
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 60 Issue 2 Pg. 95-104 (Nov 2010) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 20926261 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Autoantigens
• epiplakin
• Keratins

Topics

• Animals
• Autoantigens (physiology)
• Epidermal Cells
• Epidermis (physiology)
• Immunohistochemistry
• Keratinocytes (metabolism, physiology, ultrastructure)
• Keratins (physiology, ultrastructure)
• Mice
• Mice, Knockout
• Microscopy, Electron, Transmission
• Wound Healing (physiology)