Thymosinβ4Specific Renal Epithelial-mesenehymal Transition And The Regulating Mechanism

Background:The features of renal fibrosis is that large extracellular matrix accumulate inextracellular,including glomerular and renal tubule fibrosis. Renal fibrosis is commonpathological manifestations that various CKD progress end stage renal disease.Themorbidity of CKD increase with the number of global population aging and diabetesmellitus, obesity and hypertension increasing.Recently,much research indicated thatrenal fibrosis closely related with CKD progressing.The formation and progression ofrenal fibrosis is a complex pathological physiology process and many factors actiontogether including cell factor.Understanding the mechanism will contribute to antifibrosis treatment and delaying CKD progressing.In this case,it greatly reduced themorbidity of end stage renal disease and complication,reducing social economicburden.In recent years,people pay attention to the treatment of anti fibrosis and manymethods is still in the experimental study stage.It prove epithelial cells transdiffer tofibroblast cells or myofibroblast cells is the main mechanism of renal fibrosis andTGF-β1is the most strong induced fibrosis factor.Epithelial-mesenehymal transitioncan happen in glomerular foot cells,parietal epithelial cells and renal tubule epithelialcells.Integrin-linked kinase(ILK) is the key intracellular regulator that controlepithelial-mesenehymal transition.In addition, studies show that upregulation of ILKinduced foot cells EMT,transfertation and functional disorder by a convergingpath.The present study demonstrated in SW480colon cancer cell line thymosin beta4gene was overexpressed and accompanied morphological alteration of fibroblasts and cell-cell junctions loosing;at the same time,the expression of E－cadherindecreased obviously.E－cadherin is epithelial cell phenotypic marker protein,α-smooth muscle actin (α-SMA) is myofibroblasts main marker,loosing E－cadherinand α-SMA expression incresing are the main mark of EMT.Thymosin β4（Tβ4）is a kind of four peptide that existence effect of anti-inflammatory, angiogenesis andwound healing.Recent study found that the expression of Tβ4was Increased in EMTcells and the sclerosis glomerular,speculate that Tβ4may induced fibrosis byincresing ILK,but its degradation products N-acetyl-seryl-aspartyl-lysyl-proline(Ac-SDKP) exist anti fibrosis effects.This means that the balance between Tβ4andAc-SDKP regulate the progression of renal fibrosis.Objective:That we study the change of Tβ4expression in renal tubular epithelial cellsafter EMT and the relationship between Tβ4and Ac-SDKP is to further reveal themechanism of renal interstitial fibrosis and provide a new direction for anti fibrosisdrugs research, finaly,delaying CKD progression to chronic renal failure.Methods:A total of44people,these patient,s renal pathology was confirmed chronicpyelonephritis, FSGS, nephritis associated with interstitial fibrosis, mild lesions in ourhospital as the case group.Normal control group is8healthy persons.Detecting Tβ4content in urine by ELISA Kit; Another, choice8persons resecting renal due totraumatic with normal renal tissue as control group,we detect the expression of α-SMA and Tβ4in renal tissue by immunohistochemistry.Next we use the TGF beta1to stimulate rat renal tubular epithelial cells to induce differentiate intomyofibroblasts,then give the Ac-SDKP to interve.Finaly,detecte the change of α-SMA and Tβ4expression in cell by immunohiscytochemical,to investegate therole of Tβ4in EMT and the relationship with Ac-SDKP.We combined with clinicaldata, the determination of urinary kidney function, using SPSS software system forstatistical analysis.Results:The result of ELISA indicate that the urinary Tβ4content in case group is higher than that of normal control group,especially chronic pyelonephritis group.Renal tissue immunohistochemistry indicate the expression of α-SMA and Tβ4incase group are both higher than that of normal control group,and the difference issignificant,moreover, the dyed depth and fibrosis degree are proportional.The resultof immunohiscytochemica indicate that compare with control group, the expression ofα-SMA and Tβ4are increased significantly after TGF-β1stimulating.But aftergiving Ac-SDKP to Interve,the expression of α-SMA and T β4are bothdecressed,Ac-SDKP reduced the number of α-SMA and Tβ4positive cells in adose-dependent manner, the higher the concentration, the more apparent declinebutdid not normalize cell number.The differences among the groups is statisticallysignificant.Conclusion:The phenomenon that the expression of T β4is incresed in glomerularsclerosis,fibrosis of renal tubules,renal interstitial fibrosis and fibroblast cellsindicated that Tβ4probably induced fibrosis.it is also incresed in renal tubularepithelial cells that happened epithelial-mesenehymal transition.but after givingAc-SDKP to interve,the expression of Tβ4and α-SMA are both decressed,indicatethat Tβ4probably induced EMT,and Ac-SDKP may have negative regulatory effecton Tβ4,the relationship between them adjust the progression of renal fibrosis.