Epithelial–mesenchymal Transition of Peritoneal Mesothelial Cells Is Enhanced by M2c Macrophage Polarization
Lifang Tian, Qiaoling Yu, Dan Liu, Chen Zhao, Yuzhan Zhang, Jiamei Lu, Xiaoqin Ma, Fumeng Huang, Jin Han, Lingting Wei, Lei Zhang, Jie Gao, Li Wang, Rongguo Fu
Abstract
Background Peritoneal fibrosis (PF) can reduce the efficiency of peritoneal dialysis and eventually lead to ultrafiltration failure. Epithelial–mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is the start of PF. Macrophages are involved in the process. This study was to investigate the effect of macrophage polarization on EMT of PMCs.Methods Monocyte-macrophage cells (THP-1) were treated to induce macrophage subsets (M1, M2a, M2c). The inducing was assessed by detecting protein and mRNA expression of cytokines using ELISA and RT-PCR. Subsequently, PMCs were co-cultured with M1, M2a and M2c, respectively, in Transwell chambers for 48 h and then expressions of E-cadherin and α-SMA were determined in PMCs. The PMCs that were not co-cultured with macrophages served as control PMCs. One-way ANOVA and SNK-q test were used to conduct statistics and P < .05 as significant.Results Detection of the cytokines, including IL-6, IL-10, IL-12, TGF-β1, CCL17 and CXCL13, verified that the inducting of macrophage subtypes was successful. Compared to control, E-cadherin protein expression was significantly decreased and α-SMA protein expression increased in M1-treated PMCs (P < .05); M2a-treated PMCs had an increased gene expression of α-SMA (P < .05); E-cadherin protein and gene expression were decreased and α-SMA protein and gene expression increased significantly in M2c-treated PMCs (P < .05 or P < .01).Conclusions EMT of PMCs is enhanced by M2c macrophage polarization; meanwhile, M1 and M2a polarization may have the effect to some extent, but not as definite as M2c.