1. Tamoxifen attenuates dialysate-induced peritoneal fibrosis by inhibiting GSK-3β/β-catenin axis activation
- Author
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Huanna Tang, Jia Shen, Quanquan Shen, Wei Jin, Jiaming Zhang, Shuiyu Ji, Xiang Zhao, Pengpeng Yan, Hao Deng, Hongfeng Huang, and Xiaoying Chen
- Subjects
0301 basic medicine ,medicine.medical_treatment ,Pharmacology ,Biochemistry ,Mice ,Fibrosis ,peritoneal fibrosis ,Medicine ,Phosphorylation ,skin and connective tissue diseases ,Peritoneal Fibrosis ,Research Articles ,beta Catenin ,tamoxifen ,biology ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,epithelial-to-mesenchymal transition ,Peritoneum ,Peritoneal Dialysis ,Research Article ,medicine.drug ,Epithelial-Mesenchymal Transition ,Biophysics ,Peritoneal dialysis ,03 medical and health sciences ,Animals ,Humans ,Pyrroles ,Epithelial–mesenchymal transition ,Glycogen synthase ,Molecular Biology ,GSK3B ,Glycogen Synthase Kinase 3 beta ,business.industry ,GSK-3β ,Cell Biology ,β-catenin ,medicine.disease ,Disease Models, Animal ,Glucose ,Pyrimidines ,030104 developmental biology ,Gene Expression Regulation ,biology.protein ,Snail Family Transcription Factors ,business ,Tamoxifen - Abstract
Peritoneal fibrosis is a severe complication arising from long-term peritoneal dialysis (PD). Tamoxifen (Tamo) has been clinically proven effective in a series of fibrotic diseases, such as PD-associated encapsulating peritoneal sclerosis (EPS), but the mechanisms underlying Tamoxifen’s protective effects are yet to be defined. In the present study, C57BL/6 mice received intraperitoneal injections of either saline, 4.25% high glucose (HG) PD fluid (PDF) or PDF plus Tamoxifen each day for 30 days. Tamoxifen attenuated thickening of the peritoneum, and reversed PDF-induced peritoneal expression of E-cadherin, Vimentin, matrix metalloproteinase 9 (MMP9), Snail, and β-catenin. Mouse peritoneal mesothelial cells (mPMCs) were cultured in 4.25% glucose or 4.25% glucose plus Tamoxifen for 48 h. Tamoxifen inhibited epithelial-to-mesenchymal transition (EMT) as well as phosphorylation of glycogen synthase kinase-3β (GSK-3β), nuclear β-catenin, and Snail induced by exposure to HG. TWS119 reversed the effects of Tamoxifen on β-catenin and Snail expression. In conclusion, Tamoxifen significantly attenuated EMT during peritoneal epithelial fibrosis, in part by inhibiting GSK-3β/β-catenin activation.
- Published
- 2018