Hypoxia-induced epithelial-mesenchymal transition and fibrosis for the development of breast capsular contracture
| Autor: | Yao Lung Kuo, Jhy-Shrian Huang, Po-Wei Huang, Li-Ren Chang, Tai-I Hsu, Ting-Mao Chou, I-Ming Jou, Jian-An Chen, Seng-Feng Jeng, Chun-Hui Chu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Contracture Epithelial-Mesenchymal Transition Breast Implants lcsh:Medicine Vimentin macromolecular substances Occludin Article Mice 03 medical and health sciences 0302 clinical medicine Fibrosis Implant Capsular Contracture medicine Animals Humans Epithelial–mesenchymal transition lcsh:Science Multidisciplinary Molecular medicine biology business.industry lcsh:R Cobalt Capsular contracture Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Cell Hypoxia Extracellular Matrix Fibronectins Fibronectin Mechanisms of disease 030104 developmental biology Matrix Metalloproteinase 9 NIH 3T3 Cells biology.protein Female lcsh:Q medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-6 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-46439-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|