[Effects of overexpression of decorin on matrix metalloproteinases 2 and 9 in rat mesangial and tubular cells].
OBJECTIVE
To investigate the effects of overexpression of decorin (DCN), one of the small leucine-rich proteoglycans, on the expression of extracellular matrix molecules in glomerular mesangial and tubular cells.


METHODS
Recombinant adenovirus vector containing DCN gene (Ad/DCN) was constructed, and recombinant adenovirus containing LacZ gene (Ad/LacZ) was used as control vector. Rat renal glomerular mesangial cells of the line RMC and tubular cells of the line HK-2 were cultured and divided into following groups: high glucose + Ad/DCN transfection (experimental), high glucose + Ad/LacZ transfection (vector control), high glucose + neutralizing antibody against transforming growth factor (TGF)-beta 1 (positive control), high glucose non-transfection (PBS control), and low glucose culture (normal control) groups. Western blotting was used to detect the protein expression of decorin, TGF-beta 1, collagen type IV, MMP-2, and MMP-9.


RESULTS
The DCN protein expression was low only in the low glucose group, and was up-regulated in other groups, especially in the Ad/DCN group, so as the expression of TGF-beta 1 and collagen type IV, while the ratio of TGF-beta 1 to decorin is increased in both RMC and HK-2 cells. The expression levels of MMP-2 and MMP-9 decreased in the high-glucose-cultured RMC cells and increased in the high-glucose-cultured HK-2 cells, however, adenovirus-mediated transfection of decorin gene reversed all of these changes, and had almost the same effects on reducing the protein expression of TGF-beta 1 collagen type IV, MMP-2, and MMP-9 as anti-TGF-beta 1 antibody.


CONCLUSIONS
The agents increasing the decorin expression in mesangial and tubular cells may help prevent the development and progression of diabetic nephropathy. Overexpression of decorin may be a useful tool for developing new therapeutic application for the treatment of diabetic nephropathy.
Dong
Feng-qin
FQ
First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou 310003, China.
Li
Hong
H
Wu
Fang
F
Yao
Hang-ping
HP
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D058575:Decorin; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D050527:Mesangial Cells / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D051381:Rats
C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9