The Association Between Chemerin/ChemR23 And Endothelial-Mesenchymal Transition Of Glomeruli In Diabetic Nephropathy

BackgroundAt present,the morbidity of diabetes mellitus has been increasing year by year worldwide.Diabetic nephropathy(DN)is one of the major microvascular complications,which seriously affects the quality of life for each patient and the prognosis of the disease.It has beeen confirmed that endothelial mesenchymal transition(EndMT)is an important physiological mechanism that play a key role in the progress of diabetic nephropathy.Chemerin is a new fat factor discovered recently.Chemerin and its main ligand(ChemR23)are involved in the regulation of inflammatory response and leukocyte chemotaxis via the Chemerin/ChemR23signaling pathway.The abnormal elevation of Chemerin in the condition of disease may be associated with the transforming growth factor?1(TGF-?1),which is a key regulatory factor of EndMT.ObjectiveThe relationship between Chemerin/ChemR23 and EndMT of glomerular vascular endothelial cells(VECs)in patients with diabetic nephropathy(DN)was studied.Methods20 patients with type 2 diabetes mellitus without kidney disease were selected as diabetic group(group DM),and another 60 patients with diabetic nephropathy were selected as group DN.According to the Urinary Albumin/Creatinine Ratios(UACRs)and estimated Glomerular Filtration Rate(eGFR),the selected patients were divided into 3 subgroups:(1)group DN-A(n=20),UACR:30-300 mg/g,eGFR?60ml/(min*1.73m~2);(2)group DN-B(n=20),UACR>300mg/g,eGFR?60ml/(min*1.73m~2);(3)group DN-C(n=20),UACR>300 mg/g,eGFR<60ml/(min*1.73m~2).Last,20 healthy subjects were selected as normal control group in the experiment.The serum levels of Chemerin and TGF-?1 were detected by enzyme-linked immunosorbent assay(ELISA),and 8 renal tissue samples from DN patients identified by renal biopsy were selected,another 10 normal renal tissues as control.The immunohistochemistry was used to detect the expression levels of Chemerin,ChemR23,?-SMA,CD31 and TGF-?1 in renal tissues.qRT-PCR was used to detect the Chemerin mRNA,ChemR23 mRNA,TGF-?1 mRNA,?-SMA mRNA and CD31 mRNA in renal tissues.SPSS22.0 software was used to analyse the obtained data statistically,and the difference was considered as statistically significant when P<0.05.ResultsThe serum levels of Chemerin and TGF-?1 in patients with DM and DN were higher than those in the normal control,and the content of both was highest in group DN.There was significantly positive correlation between the expression of TGF-?1and Chemerin with the progression of DN,and the content of Chemerin and ChemR23 in the renal tissue was significantly higher in the DN patients than in the normal control.Moreover,the expression of?-SMA(fibroblast marker protein)and TGF-?1(indicators of fibrosis)in renal tissues of group DN were hjgher than those in the group NC,and the expression of CD31 in endothelial cells was lower in the group DN.Meanwhile,the mRNA expression of Chemerin,ChemR23,TGF-?1,?-SMA in group DN were higher than those in the group NC,CD31 mRNA was lower than that in the group NC.ConclusionThe degree of renal fibrosis in DN is related to the concentration of TGF-?1 in serum.With the progression of DN,endothelial cells will gradually transform into mesenchymal cells.Chemerin and ChemR23 may be involved in the development of kidney fibrosis in DN patients through regulation of EndMT.