Abstract: Objective  To investigate the role and mechanism of the suppressor of cytokine signaling 1 (SOCS1) gene in high glucose-induced epithelial-mesenchymal transformation (EMT) of peritoneal mesothelial cells in mice.  Methods  Mouse peritoneal mesothelial cells were cultured and divided into 6 groups: the control group was treated with routine medium; cells cultured in the medium containing 1.5% (83 mmol/L), 2.5% (139 mmol/L) and 4.25% (236 mmol/L) D-glucose formed the 1.5% group, 2.5% group and 4.25% group; cells transfected with negative control plasmid and cultured in the medium containing 2.5% glucose formed the 2.5%+NC plasmid group; cells transfected with SOCS1 plasmid and cultured in the medium containing 2.5% glucose formed the 2.5%+SOCS1 plasmid group. After the treatment for 24h, proliferation, migration and invasion number of the cells, mRNA expression levels of SOCS1, E-cadherin, N-cadherin and α-SMA, and JAK1/STAT1 and JAK2/STAT3 signaling pathways were detected.  Results  In 4.25% group, the proliferation level of peritoneal mesothelial cells was lower than that in control group (t=5.051, P=0.002). In 1.5%, 2.5% and 4.25% groups, the mRNA expression levels of E-cadherin and SOCS1 in peritoneal mesothelial cells were lower than those in control group (E-cadherin mRNA: t=2.774, 7.310 and 9.7813; P=0.032, ＜0.001 and ＜0.001. SOCS1 mRNA: t=2.544, 6.996 and 10.733; P=0.044, ＜0.001 and ＜0.001), while mRNA expression levels of N-cadherin and α-SMA in peritoneal mesothelial cells were higher than those in control group (N-cadherin mRNA: t=2.825, 5.121 and 7.207; P=0.030, ＜0.001 and ＜0.001. α-SMA mRNA: t=2.527, 4.807 and 6.950; P=0.045, 0.003 and ＜0.001). In 2.5%+SOCS1 plasmid group, JAK1/STAT1 and JAK2/STAT3 signaling pathways in peritoneal mesothelium cells were inhibited, the mRNA and protein expression levels of SOCS1 and the mRNA expression level of E-cadherin were higher than those in 2.5% group and 2.5%+NC plasmid group (SOCS1 mRNA: t=9.435 and 9.737, P＜0.001; SOCS1 protein: t=9.761 and 9.138, P＜0.001; E-cadherin mRNA: t=7.690 and 7.132, P＜0.001), and the number of cell migration and invasion and the mRNA expression levels of N-cadherin and α-SMA were lower than those in 2.5% group and 2.5%+NC plasmid group (t=7.350 and 8.456, P＜0.001; t=8.562 and 7.697, P＜0.001; t=4.574 and 4.865, P=0.004 and 0.003; t=3.467 and 3.036, P=0.013, 0.023).  Conclusion Overexpression of SOCS1 gene inhibits high glucose-induced EMT of peritoneal mesothelial cells in mice, which is related to the inhibition of JAK1/STAT1 and JAK2/STAT3 signaling pathways.

Key words: Peritoneal fibrosis, Peritoneal mesothelial cell, Epithelial-mesenchymal transformation, Suppressor of cytokine signaling 1