Expression Of TRPC6 In Lupus Nephritis And Its Clinical Significance

Objective: The aim of this study was to determine the expression of transient receptor potential cation channel 6(TRPC6)in the kidneys of patients with lupus nephritis(LN),to analyze its correlation with clinical and pathological indices,and to explore its possible clinical significance to provide new evidence for further elaboration of the pathogenesis and treatment of LN.Methods:(1)Patients with LN(101 cases)and 10 pathological controls with trauma or surgery who attended the Affiliated Hospital of Qingdao University from June 1,2016 to December 31,2021 were included as study subjects for retrospective study;demographic data,clinical test data and renal pathological findings of the included study subjects were collected;(2)Renal tissues of the included subjects were detected by immunohistochemical techniques.The protein levels of Nephrin,TRPC6 and LC3 II in the kidneys of the subjects were detected by immunohistochemistry,and the correlation between TRPC6 level and clinical and pathological indices was also analyzed.(3)Clinical and pathological indicators that may have an effect on 24-hour urine protein quantification were screened for proliferative LN(III,IV and with or without)using one-way linear regression analysis,and multi-factor linear regression analysis was performed to determine their independent risk factors.Results:(1)A total of 101 patients with LN were included in this study,with an average age of 30 years,and the disease occurred mostly in women of reproductive age,with a male to female ratio of about 1: 5.The main clinical manifestations of LN patients were rash,arthritis,alopecia,fever and oral ulcers,and the laboratory test characteristics were mainly hypoalbuminemia,hypocomplementation,hyperlipidemia,proteinuria,with varying degrees of hematologic involvement such as anemia.(2)The pathological types included in this study were mainly proliferative LN and membranous LN.By electron microscopic examination and pathological staining,it was observed that patients with LN had different ranges of glomerular involvement,glomerular injury,capillary hyperplasia,subepithelial and subendothelial immune complex deposition with or without mesangial lesions;there was a reduction or even fusion loss of podocyte foot process and thickening of the basement membrane.(3)Immunohistochemical results showed that the expression of TRPC6 and LC3 II was statistically elevated in kidney tissues of LN patients compared with normal kidney tissues.There were differences in TRPC6 and LC3 II expression in different pathological types,with the highest expression level in type IV LN(diffuse proliferative LN)and the lowest expression level in type V LN.(4)The results of correlation analysis showed that in proliferative LN kidneys,the mean optical density values of TRPC6 were positively correlated with 24-hour urine protein quantification,AI,capillary endothelial proliferation,and negatively correlated with ALB and C4.The protein level of TRPC6 in kidney was significantly negatively correlated with Nephrin level(r=-0.7269,P < 0.0001),while it was significantly positively correlated with LC3 II level(r=0.7797,P < 0.0001),and Nephrin was significantly negatively correlated with LC3II(r=-0.6928,P < 0.0001).(5)The results of the multifactorial linear regression model showed that TRPC6,C4,and ALB were independent risk factors for24-hour urine protein quantification in patients with proliferative LN.Conclusion:(1)TRPC6 expression levels were increased in renal tissues of patients with proliferative LN,and correlated with podocyte injury and cellular autophagy.(2)The level of TRPC6 expression in renal tissues of patients with proliferative LN was an independent risk factor for 24-hour urine protein quantification.