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.

Objective: To study the influence of recombinant human hepatocyte growth factor (rhHGF) on proliferation and extracellular matrix synthesis of autosomal dominant polycystic kidney disease (ADPKD) cyst lining epithelial cells in vitro . Methods: The effects of different concentration rhHGF (0.5,1,2.5,5 ng/ml)in 48 h and the optimal concentration rhHGF of different time (24,48,72 h ) on proliferation of ADPKD cyst lining epithelial cell lines were observed by the incorporation of 3H TdR, and synthesis of collagen and laminin were respectively observed by the incorporation of 3H proline and radioimmunoassay. Results: rhHGF stimulated the proliferation of ADPKD cyst lining epithelial cells and synthesis of collagen and laminin,the optimal concentration and time of rhHGF were 1 ng/ml and 48 h. Conclusion: rhHGF can significantly stimulate ADPKD cyst lining epithelial cells proliferation and extracellular matrix synthesis in vitro . [

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

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.

Objective To study the expression of extracellular matrix and polycystin-1 in ADPKD and their relation to cyst formation. Methods The expression of polycystin-1, fibronectin, laminin, type Ⅰ collagen, and type Ⅳ collagen were analysed in the normal kidney, fetal kidney and polycystic renal tissue by using immunohistochemical technique. Results The expression Of fibronectin, laminin, type Ⅰ collagen, and type Ⅳ collagen increased in polycystic renal tissue compared with normal kidney. The basement membrane lining cysts was markedly thickened. Type Ⅰ collagen was detected in the interstitium between cysts. Laminin, fibronectin and type Ⅳ collagen were localized in cyst basement membrane. The expression of polycystin-1 increased in polycystic renal tissue. The expression of extracellular matrix had significant correlation with the expression of polycystin-1. Conclusion The abnormal expressions of extracellular matrix and polycystin-1 exist in ADPKD. Abnormal expression of polycystin-1 may result in the alterations of extracellular matrix that is related to cyst formation.

Objective To explore the autocrine mechanism of hepatocyte growth factor (HGF) and its receptor c-MET distribution in autosomal dominant polycystic kidney disease (ADPKD) cyst-lining epithelial cells. Methods The concentration of HGF was examined with ELISA in ADPKD patients' cystic fluid, serum and cultured media of cyst-lining epithelial cells. The expression of HGF and c-MET mRNA and protein in cyst-lining epithelial cells was detected by RT-PCR, in-situ hybridization, Western blotting, immunohistochemical analysis and computer image analysis. Results The concentration of HGF in ADPKD non-dialyzed patients'cystic fluid was much higher than that in ADPKD patients' serum [(8. 61?0. 07)ng/ml vs (0.26?0.05) ng/ml, P

Objective　To observe about curative effect of MMF on type Ⅳ lupus nephritis and to review the literature about MMF used to treat LN.Method　Ten patients with type Ⅳ LN were treated with MMF 1～2 g/d plus prednisone at middle or little dose.Curative duration of these patients was between 6 and 12 months.After 3,6 and 12 months curative effect was observed.Results　After treatment proteinurie and systemic lupus activity measurement were decreased gradually.Before and after treatment ANA positive rates were 80% and 30%,anti dsDNA antibody positive rates were 50% and 10%,respectively,and low C3 and C4 was rectified.After treatment renal failure in 3 patients was recovered.During treatment major adverse reactions included gastrointestinal symptoms and herpes zoster.Conclusion　MMF has exacttly effect on type Ⅳ LN and low side effect.

Objective：To study the clinical and pathologic features of patients with lupus nephritis (LN) whose myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) were positive. Methods：The clinical and pathological features were analyzed in 18 patients with LN whose MPO-ANCA were positive. And the data of patients with different clinical outcomes were compared. Results：（1）The hematological abnormalities, hypertension and serositis in these patients were more common than general ones with LN. （2）Proteinuria and hematuria were common, the morbidities of gross hematuria and renal failure in these patients were higher than general ones with LN.（3）Various autoantibodies were positive in these patients.（4）Segmental necrosis crescentic nephritis accompanied by density of immunocomplex in glomeruli and vasculitis in intestitium were common.（5）The morbidity of ESRF and mortality of these patients were similar to general ones with LN. The morbidity of tubular atrophy in those with poor prognosis was significantly higher than those survived. Conclusion：The patients with LN whose MPO-ANCA are positive have some difference from those with negative MPO-ANCA, but positive MPO-ANCA is not directly related to the prognosis.

Objective: To obtain polycystin-1 intracellular region. Methods: cDNA of polycystin-1 intracellular region was generated by PCR and then cloned into pProEX Hta, which was prokaryotic expression vector. After verified by sequencing, the recombinant was transformed into E.coli host to express and purify the fusion protein by affinity chromatography. Results: 660 bp cDNA of polycystin-1 intracellular region and 2.6×104 fusion protein were obtained. Conclusion: The fusion protein containing polycystin-1 intracellular region is obtained and is helpful for preparing anti-polycystin-1 monoclonal antibody.

Objective To investigate the effect of over-expressed Cyr61 on the expression of extracellular matrix of human renal tubular epithelial cells(HKC), and explore the role of Cyr61 in the pathogenesis and development of autosomal dominant polycystic kidney disease(ADPKD). Methods Cyr61 gene cDNA was amplified by RT-PCR. A recombinant plasmid pcDNA3.1+ Cyr61 was constructed by cloning Cyr61 gene into pcDNA3.1. HKC cells were transfected with wild-type Cyr61 plasmid vector (pcDNA3.1+Cyr61). Then the fusion of Cyr61 gene and expression of its protein were detected by RT-PCR and Western blot. The mRNA expression of Cyr61, collagen Ⅰ, collagen Ⅳ, and laminin were determined in four groups (the untransfected cells, pcDNA3.1 transfected cells, pcDNA3.1+Cyr61 -transfected cells and cyst-lining epithelial cells) by fluorescence quantum PCR. Results The amount of Cyr61 protein in Cyr61-transfected cells and cyst-lining epithelial cells were much greater than the control. The mRNA expression of Cyr61, collagen Ⅰ, collagen Ⅳ and laminin in Cyr61-transfected cells were all amplified significantly, and the level of collagen Ⅳwas much higher than collagen I(P