In vitro characterization of the mesangial phenotype in a proliferative glomerulonephritis of the rat.
BACKGROUND
Mesangial cell proliferation is a predominant feature of many glomerular diseases. We have demonstrated in previous studies that an experimental model of mesangial-proliferative glomerulonephritis in the rat could be transferred to in vitro conditions. Using this model we now have been able to study the mesangial phenotype in several subcultures of mesangial cells from nephritic animals regarding proliferation, and the synthesis of prostaglandins and the matrix degrading enzyme MMP-2.


METHODS
Mesangial-proliferative glomerulonephritis was induced in male Sprague-Dawley rats by a single injection of an anti-Thy 1.1 antiserum. Four days after injection of the antiserum glomeruli were isolated and transferred to tissue culture conditions. Immunohistological characterization of cells, cell growth, synthesis of prostaglandins and expression of MMP-2 were studied in the first and second subculture.


RESULTS
Cells from controls and from nephritic animals showed the characteristics of glomerular mesangial cells. Proliferation was decreased in the first and second subculture of cells from nephritic rats compared with controls while there were no immunohistological differences between the cells. Biosynthesis of prostaglandin E2 was significantly increased in subcultures of mesangial cells from nephritic rats. There was also a significant increase in mRNA expression of MMP-2 in the first subculture of mesangial cells from nephritic rats when compared with controls.


CONCLUSIONS
Our data suggest that mesangial cells from nephritic animals show a different phenotype in vitro in several subcultures compared with cells from control animals. This difference can be demonstrated in the patterns of proliferation and biosynthesis of prostaglandins and MMP-2, while immunohistological characteristics of mesangial cells were unchanged between nephritic animals and controls. This experimental in vivo-in vitro approach may serve as a model to study the mesangial phenotype in glomerular diseases.
Harendza
S
S
Department of Medicine, University Hospital Eppendorf, Hamburg, Germany.
Behrens
U
U
Zahner
G
G
Schneider
A
A
Stahl
R A
RA
D000818:Animals; D002455:Cell Division / Q000502:physiology; D003094:Collagen / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D018093:Gelatinases / Q000235:genetics; D005920:Glomerular Mesangium / Q000503:physiopathology*; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D015232:Dinoprostone