Altered expression of matrix-related molecules in the development of chronic Thy1.1 nephritis.
OBJECTIVE
Matrix production and degradation are critically important in chronic nephritis. Our aim was to investigate the precise expression of matrix-related molecules which is essential for understanding the pathogenesis of renal disease.


METHODS
Chronic nephritis was induced by a single injection of anti-Thy1.1 antibody to unilaterally nephrectomized rats. RNA was extracted from renal cortex and isolated glomeruli 4, 7, and 10 weeks after the antibody injection. Matrix-related gene expressions were measured by polymerase chain reaction. The expression of alpha1(IV) and alpha3(IV) collagens was studied by immunohistochemistry. The gelatinolytic activity in the glomeruli was assayed by gelatin zymography.


RESULTS
Polymerase chain reaction revealed an increase of alpha1(IV) in both glomeruli and renal cortex from nephritic rats. In contrast, the expression of alpha3(IV), normally a component of the glomerular basement membrane, was decreased in nephritic animals. Immunohistochemistry confirmed the finding that alpha1(IV) and alpha3(IV) were up- and downregulated, respectively, in the glomeruli. Gene expression and activity of matrix metalloproteinase 2 were enhanced, while those of matrix metalloproteinase 9 were clearly suppressed in nephritis.


CONCLUSIONS
Downregulation of alpha3(IV) and enhancement of the matrix metalloproteinase-2 activity in the glomeruli may contribute to the glomerular damage by altering the glomerular basement membrane components. Impairment of the glomerular basement membrane integrity may possibly be implicated in irreversible renal dysfunction.
Kuroda
Takayuki
T
Discovery Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. takayuki.kuroda@shionogi.co.jp
Tanioka
Hideki
H
Masui
Masao
M
Ito
Masashi
M
Notoya
Mitsuru
M
Shinosaki
Toshihiro
T
D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis; D024141:Collagen Type IV / Q000096:biosynthesis; D024062:Collagen Type V / Q000096:biosynthesis; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D050533:Glomerular Basement Membrane / Q000503:physiopathology; D005921:Glomerulonephritis / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
D024042:Collagen Type I; D024141:Collagen Type IV; D024062:Collagen Type V; D016326:Extracellular Matrix Proteins; D018800:Thy-1 Antigens; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9