Hypoxia-induced epithelial-mesenchymal transition and fibrosis for the development of breast capsular contracture

Yao Lung Kuo, I. Ming Jou, Seng Feng Jeng, Chun Hui Chu, Jhy Shrian Huang, Tai I. Hsu, Li Ren Chang, Po Wei Huang, Jian An Chen, Ting Mao Chou

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Abstract

Fibrosis has been considered as a major cause of capsular contracture. Hypoxia has widely emerged as one of the driving factors for fibrotic diseases. The aim of this study was to examine the association between hypoxia-induced fibrosis and breast capsular contracture formation. Fibrosis, epithelial-mesenchymal transition (EMT), expression levels of hypoxia-inducible factor-1α (HIF-1α), vimentin, fibronectin, and matrix metalloproteinase-9 (MMP-9) in tissues from patients with capsular contracture were determined according to the Baker classification system. Normal breast skin cells in patients with capsular contracture after implant-based breast surgery and NIH3T3 mouse fibroblasts were cultured with cobalt chloride (CoCl2) to mimic hypoxic conditions. Treatment responses were determined by detecting the expression of HIF-1α, vimentin, fibronectin, N-cadherin, snail, twist, occludin, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2, as well as phosphorylated ERK. The expression levels of HIF-1α, vimentin, fibronectin, and fibrosis as well as EMT were positively correlated with the severity of capsular contracture. MMP-9 expression was negatively correlated the Baker score. Hypoxia up-regulated the expression of HIF-1α, vimentin, fibronectin, N-cadherin, snail, twist, TIMP-1 and -2, as well as phosphorylated ERK in normal breast skin cells and NIH3T3. Nonetheless, the expression levels of MMP-9 and occludin were down-regulated in response to CoCl2 treatment. This study is the first to demonstrate the association of hypoxia-induced fibrosis and capsular contracture.

Original languageEnglish
Article number10269
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

All Science Journal Classification (ASJC) codes

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    Kuo, Y. L., Jou, I. M., Jeng, S. F., Chu, C. H., Huang, J. S., Hsu, T. I., Chang, L. R., Huang, P. W., Chen, J. A., & Chou, T. M. (2019). Hypoxia-induced epithelial-mesenchymal transition and fibrosis for the development of breast capsular contracture. Scientific reports, 9(1), [10269]. https://doi.org/10.1038/s41598-019-46439-7