上皮角質(zhì)形成細(xì)胞增殖,是創(chuàng)面修復(fù)必不可少的因素,，而上皮細(xì)胞增殖異常是皮膚疾病銀屑病的內(nèi)在原因。這些炎癥過程中上皮細(xì)胞增殖的觸發(fā)因子尚未完全理解,。
本研究表明,，再生性胰島起源蛋白3α（REG3A）在銀屑病、創(chuàng)面修復(fù)以及咪喹莫特誘導(dǎo)銀屑病皮損情況下的角質(zhì)細(xì)胞中高度表達(dá),。
研究還發(fā)現(xiàn),，白細(xì)胞介素17（IL-17）通過活化角質(zhì)細(xì)胞編碼的IL-17受體A（IL-17RA）誘導(dǎo)角質(zhì)細(xì)胞表達(dá)。REG3A結(jié)合exostosin樣3蛋白（EXTL3）進(jìn)而激活磷酸肌醇3激酶（PI3K）和激酶Akt,，從而抑制角質(zhì)細(xì)胞的終末分化并增加細(xì)胞增殖,。
這些研究結(jié)果顯示，REG3A,，一種腸道分泌的抗菌蛋白,，能促進(jìn)皮膚角質(zhì)形成細(xì)胞增殖,，并受IL-17誘導(dǎo),。這一研究表明，REG3A可能介導(dǎo)在正常創(chuàng)面修復(fù)和銀屑病條件下的表皮增生,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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PMID:
The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury
Yuping Lai, Dongqing Li, Changwei Li, Beda Muehleisen, Katherine A. Radek, Hyun Jeong Park, Ziwei Jiang, Zhiheng Li, Hu Lei, Yanchun Quan, Tian Zhang, Yelin Wu, Paul Kotol, Shin Morizane, Tissa R. Hata, Keiji Iwatsuki, Ce Tang, Richard L. Gallo
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.
