The Effect Of Toll-like Receptor-4(TLR4)and It’s Regulatory Factor-suppressor Of Cytokine Signaling-3(SOCS3) In The Pathogenesis Of IgA Nephropathy

Objective：To explore the effect of Toll-like receptor-4(TLR4) and it’s regulatoryfactor-suppressor of cytokine signaling-3(SOCS3) in the immunological mechanismof IgAnephropathy(IgAN).Methods：21IgAN patients and21normal subjects were researched. All patients werepathologic diagnosed primary IgA nephropathy excluding secondary reasons．None ofthe patients have been treated with glucocorticoid or immunosuppressants in onemonth．The PBMC of IgAN patients and normal controls were separated by Ficollmethod. Detecting the mRNA levels of TLR4and SOCS3by real-time polymerasechain reaction. The TLR4and SOCS3protein levels were detected by westernblotting. Immunohistochemical staining was used to explor the difference of TLR4and SOCS3in the renal tissues of IgAN patients and normal subjects.Results：（1）Real-time PCR and Western blotting showed that TLR4and SOCS3mRNAand protein levels of IgAN patients were higer than normal control group,especiallythe TLR4protein expression in the PBMC of IgAN patients increased significantly,the difference was statistically significant (P <0.01). The level of SOCS3proteinrelatived to the level of TLR4protein expressed in the PBMC of IgAN patients.Butneither the genetic level nor the protein level,there was no obvious correlation withclinical indexes.（2）Immunohistochemical staining showed that there were little expression ofTLR4and SOCS3in normal glomeruli and renal tubules, in the IgAN patients,expression was significantly higher. In the patients with IgAN, correlation analysisshowed that the mean density of TLR4in the renal tubules are positively related withserum creatinine,urea blood urea nitrogen, blood uric acid, negatively related with glomerular filtration rate. The mean density of SOCS3in the glomerular positivelyrelationed with24-hours proteinuria, negatively relationed with blood albumin. Themean density of SOCS3of the renal tubules are positively related with urine occultblood.Conclusion:The expression of TLR4and SOCS3in the PBMC and renal tissues of IgANpatients were higher than normal control group, and positively related to the degree ofkidney damage, indicating that TLR4and SOCS3may participate in the developmentof IgAN.