Effect of heparin on Janus kinase-signal transducer and activator of transcription signaling pathway and hemoglobin levels in a Kawasaki disease mouse model
Objective To investigate the effect of heparin on the regulation of Janus kinase-signal transducer and activator of transcription(JAK-STAT)signaling pathway and its impact on hemoglobin levels in a Kawasaki disease(KD)mouse model.Methods Forty-five C57 mice were randomly divided into three groups:the control group,the model group,and the heparin treatment group,with 15 mice in each group.The KD model was induced by the water-soluble components of Candida albicans cell wall.The control and model groups received 0.9%sodi-um chloride solution(0.05 mL/g),while the heparin treatment group was administered heparin(0.1 U/g),both by in-traperitoneal injections once daily for 7 days.Body weight and hemoglobin levels were monitored.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of serum interleukin-6(IL-6)and hepcidin in the mice.Western blot was used to detect the expression of JAK-STAT signaling pathway-related proteins in the liver tissues,and real-time quantitative PCR was used to assess the mRNA levels of these proteins.Results Compared with the control group,the model group showed a decrease in body weight and hemoglobin levels,along with in-creased serum IL-6 and hepcidin levels.The model group also showed upregulated expression of JAK1,phosphory-lated JAK1(p-JAK1),JAK2,phosphorylated JAK2(p-JAK2),STAT3,and phosphorylated STAT3(p-STAT3)proteins in liver tissues.Additionally,the mRNA levels of JAK1,JAK2,and STAT3 were also upregulated.Compared with the model group,the heparin treatment group showed a significant increase in body weight[Day 26:(27.11±0.58)g vs.(21.29±0.39)g,P<0.05]and hemoglobin levels[Day 26:(150.65±9.53)g/L vs.(102.61±8.030)g/L,P<0.05],along with decreased serum IL-6[Day 26:(36.73±3.40)pg/mL vs.(68.05±5.20)pg/mL,P<0.05]and hepcidin levels[Day 26:(167.49±10.72)ng/mL vs.(332.93±15.99)ng/mL,P<0.05].The heparin treatment group also showed down-regulated expression of JAK1[(0.26±0.02)vs.(1.27±0.07),P<0.05],p-JAK1[(0.31±0.04)vs.(1.30±0.09),P<0.05],JAK2[(0.47±0.05)vs.(1.27±0.07),P<0.05],p-JAK2[(0.45±0.05)vs.(1.14±0.08),P<0.05],STAT3[(0.64±0.04)vs.(1.11±0.08),P<0.05),and p-STAT3[(0.46±0.04)vs.(1.09±0.07),P<0.05]proteins in liver tissues.Additionally,mRNA levels of JAK1[(1.38±0.10)vs.(3.05±0.23),P<0.05],JAK2[(1.42±0.09)vs.(3.82±0.50),P<0.05],and STAT3[(1.95±0.12)vs.(4.58±0.34),P<0.05]were also downregulated.Conclusion Heparin can effectively increase hemoglobin levels in KD model mice,and its mechanism may be related to the regulation of the JAK-STAT sig-naling pathway and the reduction of hepcidin levels.
MouseKawasaki diseaseJanus kinase-signal transducer and activator of transcription signaling pathwayHepcidinHemoglobin
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