The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury.
The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury.
复制标题
抗菌蛋白REG3A调节皮肤损伤后角质形成细胞增殖和分化。
DOI：
10.1016/j.immuni.2012.04.010
复制
发表时间：
2012-07-27
期刊：
影响因子：
32.4
通讯作者：
Gallo RL
中科院分区：
文献类型：
--
作者：
Lai Y;Li D;Li C;Muehleisen B;Radek KA;Park HJ;Jiang Z;Li Z;Lei H;Quan Y;Zhang T;Wu Y;Kotol P;Morizane S;Hata TR;Iwatsuki K;Tang C;Gallo RL
表皮角质形成细胞增殖是伤口修复的基本要素，而异常的上皮增殖是皮肤病银屑病的内在要素。在这些炎症过程中触发上皮细胞增殖的因素还不完全清楚。在这里，我们已经表明，再生胰岛衍生蛋白3-α（REG 3A）是高度表达的角质形成细胞在银屑病和伤口修复和咪喹莫特诱导的银屑病皮肤病变。由角质形成细胞表达的REG 3A由白细胞介素-17（IL-17）通过激活角质形成细胞编码的IL-17受体A（IL-17 RA）诱导，并反馈角质形成细胞以抑制终末分化并通过结合外生肌纤维素样3（EXTL 3）随后激活磷脂酰肌醇3激酶（PI 3 K）和激酶AKT来增加细胞增殖。这些发现表明，REG 3A，一种分泌的肠道抗菌蛋白，可以促进皮肤角质形成细胞增殖，并可以由IL-17诱导。这一观察结果表明，REG 3A可能介导在正常伤口修复和银屑病中观察到的表皮过度增殖。
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 kerati-nocytes 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.
登录
查看更多内容
影响因子：
64.8
作者：
Brandl, Katharina;Plitas, George;Mihu, Coralia N.;Ubeda, Carles;Jia, Ting;Fleisher, Martin;Schnabl, Bernd;DeMatteo, Ronald P.;Pamer, Eric G.
通讯作者：
Pamer, Eric G.
影响因子：
3.8
作者：
Finnerty, Celeste C.;Przkora, Rene;Herndon, David N.;Jeschke, Marc G.
通讯作者：
Jeschke, Marc G.
影响因子：
100.3
作者：
Dong, C
通讯作者：
Dong, C
DOI：
10.1073/pnas.91.23.11035
发表时间：
1994-11-08
影响因子：
11.1
作者：
GALLO, RL;ONO, M;BERNFIELD, M
通讯作者：
BERNFIELD, M
影响因子：
4.6
作者：
Croyle, Mandy J.;Lehman, Jonathan M.;Yoder, Bradley K.
通讯作者：
Yoder, Bradley K.