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WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury

Title
WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury
Authors
Jeong H.Lee B.Kim K.H.Cho S.Y.Cho Y.Park J.Lee Y.Oh Y.Hwang B.R.Jang A.-R.Park J.-H.Jeong S.-H.Lee D.Lee Y.C.Lim K.-M.Goldenring J.R.Nam K.T.
Ewha Authors
이대기임경민
SCOPUS Author ID
이대기scopus; 임경민scopus
Issue Date
2021
Journal Title
Gastroenterology
ISSN
0016-5085JCR Link
Citation
Gastroenterology vol. 161, no. 3, pp. 953 - 9.67E17
Keywords
Interleukin-33 (IL33)M2 macrophageSPEMWFDC2
Publisher
W.B. Saunders
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Background & Aims: WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, 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 with the use of preneoplastic metaplasia models. Methods: Three spasmolytic polypeptide–expressing metaplasia (SPEM) models were established in both 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. Results: Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. Conclusions: WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis. © 2021 AGA Institute
DOI
10.1053/j.gastro.2021.05.058
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자연과학대학 > 생명과학전공 > Journal papers
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