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Objective:To investigate characteristic expression of TGF-?1 in human ADPKD and clarify its role in the development and progression of human ADPKD. Methods:Cyst fluid, urinary and plasma TGF-?1 levels were determined by ELISA in 39 ADPKD patients. The results were compared with those of normal subjects and of patients with simple renal cyst. TGF-?1, TGF-?1 receptors types Ⅰ, types Ⅱ, CTGF mRNA and proteins in the kidneys of human ADPKD were examined by in situ hybridization and immunohistochemistry. The relationship of the above fibrosing-associated indicators with the degree of interstitial fibrosis was analyzed. Results:Plasma TGF-?1 level was the highest among body fluids. In ADPKD and simple renal cyst, TGF-?1 levels were significantly higher than those in normal subjects (15.12 ?8.53)?g/L vs (5.41?1.31) ?g/L,P
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Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease,its prevalence ranges from 1 in 1 000 to 1 in 400.Two genes responsible for ADPKD, PKD 1 and PKD 2,were cloned in 1994 and 1996 respectively. Many researches have been done and great progress has been made on ADPKD.Current hot issues in this area included the structures and functions of polycystin 1 and polycystin 2,the role of cilia on polycystic kidney disease(PKD),the relationship between polycystins and the vascular abnormalities,the image evaluation of PKD,the effects of blocking RAS on slowing down the PKD progression and the treatment prospects for ADPKD. This paper focused on some issues and their implications for the diagnosis and treatment of PKD.
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Objective:To study the effects of recombinant human hepatocyte growth factor (rhHGF) on the synthesis of extracellular matrix (ECM) and matrix metalloproteinases and tissue inhibitor of metalloproteinases in autosomal dominant polycystic kidney disease (ADPKD) cyst lining epithelial cells.Methods:The synthesis of laminin (LN) and aminoterminal propeptide of type Ⅲ procollagen (PⅢNP) in ADPKD cyst lining epithelial cells stimulated by rhHGF was examined with radioimmunoassay.The synthesis of type Ⅳ collagen (ColⅣ) was analyzed with ELISA.The mRNA expression of transforming growth factor ? 1 (TGF? 1),matrix metalloproteinases 2 (MMP 2),tissue inhibitor of metalloproteinases 1 (TIMP 1) and TIMP 2 in rhHGF stimulated cyst lining epithelial cells were detected by RT PCR.MMP 2 protein expression was examined with Western blotting and MMP 2 activity was analyzed by gelatin zymography in supernatant of cyst lining epithelial cells stimulated by rhHGF.Results:In rhHGF group and rhHGF+ anti TGF? 1 antibody group,the synthesis of LN and ColⅣ were markedly increased.There was no significant difference in the synthesis of LN and ColⅣ between the 2 groups.Among control group,rhHGF group,rhHGF+ anti HGF antibody group and rhHGF+ anti TGF? 1 antibody group,no significant difference in the synthesis of PⅢNP was found.No significant difference was found in the expression level of TGF? 1 mRNA in cyst lining epithelial cells among control group,rhHGF group and rhHGF+anti HGF antibody group.Compared with control group,MMP 2 mRNA expression in ADPKD cyst lining epithelial cells was significantly increased and TIMP 1 mRNA and TIMP 2 mRNA expression were significantly decreased in rhHGF group.Furthermore,MMP 2 protein expression and MMP 2 activity in supernatant of cyst lining epithelial cells also greatly increased.Conclusion:HGF stimulates the synthesis of LN and ColⅣ.HGF up regulates MMP 2 expression while HGF down regulates TIMP 1 and TIMP 2 expression in ADPKD cyst lining epithelial cells.All these changes may involve in the initiation and progression of ADPKD cysts.
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Objective: To study the effect of N (4 hydroxyphenyl) retinamide (4 HPR) on apoptosis of cyst lining epithelial cells in autosomal dominant polycystic kidney disease (ADPKD).Methods: The proliferation of ADPKD cyst lining epithelial cells was detected by MTT assay after stimulated by 1,2.5,5 and 10 ?mol/L 4 HPR for 24,48,72 and 96 h respectively.The effect of 4 HPR on the survival rate of cells stimulated by HGF was analyzed with trypan blue staining.The effect of 4 HPR on the apoptotic rate of cyst lining epithelial cells stimulated by HGF was detected with DNA laddering and cell staining with fluorescent dye Hoechst 33342.The expression of HGF and c Myc protein was examined by immunohistochemical staining and semi quantitative analysis in cyst lining epithelial cells stimulated by 4 HPR.Results: Compared with control group,4 HPR inhibited the proliferation of ADPKD cyst lining epithelial cells in a dose and time dependent manner.The most remarkable inhibition effect was observed by 5 or 10 ?mol/L 4 HPR for 96 h ( P