WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury.
WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury.
复制标题
WFDC2通过上调IL 33促进痉挛性多肽表达的化生，以响应损伤。
DOI：
10.1053/j.gastro.2021.05.058
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发表时间：
2021-09
期刊：
影响因子：
29.4
通讯作者：
Nam KT
中科院分区：
文献类型：
--
作者：
Jeong H;Lee B;Kim KH;Cho SY;Cho Y;Park J;Lee Y;Oh Y;Hwang BR;Jang AR;Park JH;Park JH;Jeong SH;Lee D;Lee YC;Lim KM;Goldenring JR;Nam KT
WAP four-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4 (HE4), is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis using preneoplastic metaplasia models. Three spasmolytic polypeptide-expressing metaplasia (SPEM) models were established each in wild-type and Wfdc2-knockout mice, with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens. Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2 type macrophages in all three SPEM models. Transcriptomic analysis revealed that Wfdc2 knockout prevented the upregulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of rWFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with rWFDC2 was able to induce SPEM development. WFDC2 expressed in response to gastric injury promotes SPEM through the upregulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis. WFDC2 expression is upregulated in the tissue and gastric juice of preneoplastic metaplasia and gastric cancer. Wfdc2 knockout protected against spasmolytic polypeptide-expressing metaplasia (SPEM) in mice while the exogenous supplementation of rWFDC2 recovered SPEM development. rWFDC2 increased IL33 expression, which subsequently induced M2 macrophage polarization. Most importantly, long-term treatment of rWFDC2 could induce SPEM development alone, indicating the pivotal role of WFDC2 in early gastric carcinogenesis.
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影响因子：
29.4
作者：
Huh WJ;Khurana SS;Geahlen JH;Kohli K;Waller RA;Mills JC
通讯作者：
Mills JC
影响因子：
5.4
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Liang Y;Jie Z;Hou L;Yi P;Wang W;Kwota Z;Salvato M;de Waal Malefyt R;Soong L;Sun J
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Sun J
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Liew, Foo Y.
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82.9
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--
影响因子：
29.4
作者：
Burclaff J;Osaki LH;Liu D;Goldenring JR;Mills JC
通讯作者：
Mills JC