Effects of hepatocyte growth factor on synthesis of extracellular matrix and matrix metalloproteinases and tissue inhibitor of metalloproteinases in autosomal dominant polycystic kidney disease cyst-lining epithelial cells
- VernacularTitle:肝细胞生长因子对ADPKD囊肿衬里上皮细胞合成细胞外基质、基质金属蛋白酶及其抑制剂的作用(英文)
- Author:
Aihong YUAN
;
Changlin MEI
;
- Publication Type:Journal Article
- Keywords:
hepatocyte growth factor;
polycystic kidney disease, autosomal dominant;
extracellular matrix
- From:
Academic Journal of Second Military Medical University
1982;0(01):-
- CountryChina
- Language:Chinese
-
Abstract:
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.
