| OBJECTIVE: Proliferation of mesangial cells and ECM accumulation leading to glomerulosclerosis is central feature of progressive glomerulonephritis. Understanding the regulatory mechanisms involved in mesangial cells proliferation is necessary. Augmenter of liver regeneration (ALR) from the liver is a new growth factor that can promote hepotocyte regeneration and prevent liver fibrosis. Biological action of ALR is unclear though it is high level in the kidney. HPN is a low molecular weight polypeptide and is similar to ALR in many effects. Our previous experiment in vitro has been shown: rrALR can promote the proliferation of rat mesangial cells and secretion of TGF-β induced by IL-1. High concentration HPN can inhibit the proliferation of rat mesangial cells. In order to investigate the roles of ALR and HPN in the progression of glomerulonephritis, we examined the expression of ALR in the kidney of normal and anti-Thy1.1 glomerulonephritis rats and observed the effects of ALR and HPN on the GMCs proliferation and ECM accumulation in anti-Thy1.1 glomerulonephritis rats. METHODS:(1) The modle of anti-Thy1.1 nephritis were induced by a single intravenous administration of ATS. (2) Urine examination, BUN & Scr were detected by common methods.(3) Proteinuria in 24h was detected by the method of bi-wavelength. (4) PAS and HE stain were used to detect the pathological characters of anti-Thy1.1 nephritis.(5) Immunohistochemistry and Western blot were used to detect the expression of ALR and PCNA in vivo.(6) The pathological feature of glomeruli and the results of Western blot was analysised with the image analytical software.(7) Rats in ALR group were injected rrALR into peritoneal cavity with the dosage of 50μg/kg.d. Rats in HPN group were injected HPN into muscle with the dosage of 5mg/kg.d. BUN, Scr, proteinuria and the pathological feature of glomeruli were detected by the same methods.RESULTS: (1) The modle of anti-Thy1.1 nephritis were confirmed by the changes of proteinuria and pathological feature of glomeruli.(2) In the kidney of normal rat, expressive distribution of ALR is in the epithelial cells of renal tubules and collecting duct in medulla. (3) In anti-Thy1.1 nephritis rat, the distribution of ALR expression is notonly in medulla but also in some tubules near the cortical glomeruli , its level is markedly increased. Change of ALR expression is relevant to the proliferation of megangial cells. (4) rrALR didn't show the effects on proteinuria, GMCs proliferation and ECM expansion of anti-Thy1.1 nephritis rats by intra-peritoneal cavity injection with the dosage of rrALR 50μg/kg.d during acute phase(P＞0.05).(5) Proteinuria, GMCs proliferation and ECM expansion of anti-Thy1.1 nephritis rat with by intramuscular injection the dosage of 5mg/kg.d has been reduced(P＜0.05). CONCLUSION: (1) At the first time, we observed expression of ALR in the kidney of normal rats is in renal tubular epithelial cells and collecting duct. (2) In anti-Thy1.1 nephritis rats, the distribution of ALR expression is not only in medulla but also in some tubules near the cortical glomeruli, its level is markedly increased. Change of ALR expression is relevant to the proliferation of megangial cells. (3) Effect of ALR was not shown on mesangial cells proliferation, mesangial matrix expansion and proteinuria in group of anti-Thy1.1 nephritis rats with the dosage of rrALR 50μg/kg.d by I.P.(4) HPN reduced GMCs proliferation, ECM expansion and proteinuria in group of anti-Thy1.1 nephritis rats with the dosage of HPN 5mg/kg.d.(5) HPN has various functions in different organs but no specifity in species.
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