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Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

Authors:

Xingzhe Ma, Rong Xiang, Jihong Han et al.

Citation:

Biochimica et Biophysica Acta 1852 (2015) 1038–1048

Abstract:

Hernia is a disease with defects in collagen synthesis/metabolism. However, the underlying mechanisms for hernia formation have not been fully defined. Tamoxifen is a selective estrogen receptor modulator and used for patients with breast cancer. Tamoxifen also has pleiotropic and side effects. Herein, we report that tamoxifen treatment resulted in an appearance of a large bulge in the lowabdomen between the hind legs inmale but not in female mice. The autopsy demonstrated that the lowabdominal wall was broken and a large amount of intestine herniated out of the abdominal cavity.Histological analysis indicated that tamoxifen caused structural abnormalities in the low abdominal wall which were associated with decreased type II collagen content. Furthermore, we determined increased matrix metalloproteinase-2 (MMP-2) and MMP-13 expression in the tissue. In vitro, tamoxifen induced MMP-2 and MMP-13 expression in fibroblasts. The promoter activity analysis and ChIP assay demonstrate that induction of MMP-13 expression was associated with activation of JNK–AP-1 and ERK1/2 signaling pathwayswhile induction ofMMP-2 expressionwas related to activation of the ERK1/2 signaling pathway. Taken together, our study establishes a novel murine hernia model, defines a severe side effect of tamoxifen, and suggests a caution to male patients receiving tamoxifen treatment.

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