Prohibitin Levels In Blood: The Marker Of Early Renal Tubularinterstitial Damage

Objective:Renal interstitial fibrosis(RIF) determines onset and progression of chronic renal failure in most renal diseases.RIF is a common character in end-stage renal diseases.In the previous research works of our group,Huang et al showed that prohibitin(PHB),a protein with cell-cycle regulatory activity,was down-regulated by 50%in renal tissue of RIF rats induced by UUO with gene expression microarray analysis.As a potential tumor suppressor,PHB was first known to inhibit cell proliferation by repressing E2F-mediated transcription.Previous works showed that PHB protein was positively expressed at normal renal tissues and negatively correlated with the degrees of tubulointerstitial lesions.Furthermore,over-expression of PHB suppresses renal interstitial fibroblasts proliferation and cell phenotypic change induced by TGF-β1,which indicates PHB as a potential therapeutic target to halt the progression of TIF.Research in recent years has shown that prohibitin was also a blood-borne tumor antigen whose expression is increased in the blood of tumor patients.Thus we wonder the serum prohibitin protein level of patients with kidney disease might also has a potential correlation with the degree of RIF.Methods:The serum PHB protein levels were determined by Western Blot analysis in children with kidney diseases(36 cases) as well as healthy children(30 cases). Levels of BUN,Scr,urinary microprotein were detected by the automatic biochemical analyzer.Renal interstitial damage was semiquantitatively graded according to Katafuchi's study.The correlation between the levels of serum PHB protein and the levels of BUN,Scr as well as urine microprotein were statistical analysis.Results:Serum PHB protein could be positively detected in chilren with diverse kidney diseases compared to healthy children.The serum PHB levels in children with proliferative glomerulonephritis were significantly higher than those with non-proliferative glomerulonephritis(P＜0.05).Statistical Analysis indicated the positively correlation between the serum PHB levels and the degrees of tubulointerstitial lesions(r=0.868,P＜0.001) as well as glomerular injury(r=0.753, P＜0.001).Furthermore,it was found that serum PHB levels were also positively correlated with the urinary microprotein including NAG(r=0.586,P＜0.001) and IgG (r=0.341,P＜0.001).Conclusion:In this study,we found that serum PHB was significantly increased in children with kidney diseases.There was positive correlation between serum PHB levels and degrees of renal interstitial damage.Serum PHB levels might be a potential clinical index for tubulointerstitial lesions.