The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury.

Abstract

Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.

DOI: 10.1016/j.immuni.2012.04.010

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@article{Lai2012TheAP, title={The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury.}, author={Yuping Lai and Dongqing Li and Changwei Li and Beda Muehleisen and Katherine A. Radek and Hyun Jeong Park and Ziwei Jiang and Zhiheng Li and Hu Lei and Yanchun Quan and Tian Shu Zhang and Yelin Wu and Paul F. Kotol and Shin Morizane and Tissa R. Hata and Keiji Iwatsuki and Ce Tang and Richard L Gallo}, journal={Immunity}, year={2012}, volume={37 1}, pages={74-84} }