The Effects Of Human Serum Albumin On Expression Of ACE2 In The Proximal Tubular Cells

Background and Objective:The appearance of proteinuria has been seen most in nephropathy.It is not only an index of pathological changes in kidney diseases,but also promotes the process of renal pathological changes as an independent factor.Albumin is the major component of proteinuria,which can injury proximal tubular cell.Renin angiotensin system(RAS) plays an important role in the progression of kidney diseases.As a new member of RAS,Angiotensin converting enzyme 2(ACE2) counterbalances Angiotensin converting enzyme(ACE) by promoting vasodilatation and benefiting renal protection.In kidney,the expression of ACE2 was manly found in proximal tubular cell.The proximal tubular cells of patients with proteinuria are in a state with high concentration of albumin,which can induce activation of proximal tubular cell.High concentration of albumin may promote the progession of kindey disease by decrease the expression of ACE2.In order to validate the hypothesis,we try to study the effects of human serum albumin on gene and protein expression of ACE2 and ACE in the proximal tubular cells,so as to explore the mechanism of renal injure caused by albumin or albuminuria.Methods:The normal human proximal tubular cells(HK-2) cultured in vitro were used in experiment at psssage numbers seventh.HK-2 was incubated in serum-free medium for 24 hours after sub-confluent culture,and then exposed to albumin in diffent concentrations(0,1,5,10,15g/L) for 48 hours.The expressions of ACE2 and ACE mRNA in HK-2 were tested by RT-PCR method and the expression of ACE2 and ACE protein tested by Western blot method.Results:The mRNA and protein expression of ACE2 and ACE existed in nomal cultured HK-2.Albumin(1g/L-15g/L) inhibited the expression of ACE2 mRNA and protein in HK-2 cells in a dose-dependent manner.Albumin in 5 g/L concentration inhibited significantly the mRNA and protein expression of ACE2 in HK-2 in comparison with normal control group(P＜0.01).The expression of ACE in mRNA and protein was at a relative low level in normal HK-2 cells.Albumin increased the expression of ACE in mRNA and protein in HK-2 cells in a dose-dependent manner. Albumin in 10 g/Lconcentration increased significantly the expression of ACE in mRNA and protein in HK-2 cells in comparison with normal control group(P＜0.05).Conclusion:The mRNA and protein expression of ACE and ACE2 exists in HK-2 cells cultured in vitro.Human serum albumin can inhibit the expression of ACE2 and increase the expression of ACE in cultured HK-2 cells,which may be one of mechanisms of that albumin contributes to pathological changes,such as the tubulointerstitial injury,glomerular sclerosis and interstitial fibrosis.