The role and mechanism of SOCS1 gene in high glucose-induced epithelial-mesenchymal transforma-tion of peritoneal mesothelial cells in mice
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 mesotheli-al 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 con-taining 2.5％glucose formed the 2.5％+SOCS1 plasmid group.After the treatment for 24h,proliferation,mi-gration 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 mesotheli-al 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 ex-pression 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 in-vasion 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.
Peritoneal fibrosisPeritoneal mesothelial cellEpithelial-mesenchymal transformationSuppressor of cytokine signaling 1
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