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Association of a decreased number of d(CA) repeats in the matrix metalloproteinase-9 promoter with glomerulosclerosis susceptibility in mice

FORNONI, Alessia ; YINGCAI WANG ; LENZ, Oliver ; STRIKER, Liliane J ; STRIKER, Gary E

Journal of the American Society of Nephrology, 2002-08, Vol.13 (8), p.2068-2076 [Periódico revisado por pares]

Hagerstown, MD: Lippincott Williams & Wilkins

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Título:
Association of a decreased number of d(CA) repeats in the matrix metalloproteinase-9 promoter with glomerulosclerosis susceptibility in mice
Autor: FORNONI, Alessia ; YINGCAI WANG ; LENZ, Oliver ; STRIKER, Liliane J ; STRIKER, Gary E
Assuntos: Animals ; Base Sequence - genetics ; Biological and medical sciences ; Cells, Cultured ; Dinucleotide Repeats ; Genetic Predisposition to Disease - genetics ; Glomerulonephritis ; Glomerulosclerosis, Focal Segmental - genetics ; Matrix Metalloproteinase 9 - genetics ; Medical sciences ; Mice ; Molecular Sequence Data ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Polymorphism, Genetic - genetics ; Promoter Regions, Genetic - drug effects ; Promoter Regions, Genetic - genetics ; RNA, Messenger - metabolism ; Tetradecanoylphorbol Acetate - pharmacology ; Transcription, Genetic - genetics
É parte de: Journal of the American Society of Nephrology, 2002-08, Vol.13 (8), p.2068-2076
Descrição: The genetic background plays an important role in the development of progressive glomerulosclerosis. However, no marker is available for the reliable prediction of genetic susceptibility to glomerulosclerosis. Because matrix metalloproteinase-9 (MMP-9) levels are decreased in models of glomerulosclerosis and MMP-9 promoter polymorphism has been observed among patients with diabetic nephropathy, MMP-9 could be one such marker. The object of this study was to determine whether MMP-9 promoter polymorphism was associated with altered MMP-9 expression in mesangial cells (MC) from two mouse strains, i.e., ROP (glomerulosclerosis prone) and B6SJL (glomerulosclerosis resistant). ROP MC expressed 12-fold less MMP-9 mRNA. The MMP-9 promoter in ROP MC contained fewer d(CA) repeats, which was associated with lower MMP-9 expression and activity. Phorbol-12-myristate-13-acetate (3 to 60 ng/ml) increased MMP-9 expression in both MC types (3- to 4.5-fold), but the level in ROP MC never reached that in B6SLJ MC. Although reciprocal transfection of ROP and B6SJL MMP-9 promoter constructs into B6SJL and ROP cells revealed that the promoters were functional in both cell types, the B6SJL promoter was less responsive to phorbol-12-myristate-13-acetate stimulation when transfected into ROP MC, suggesting a role for other factors. In conclusion, the MMP-9 promoter exhibits a decreased number of d(CA) repeats in the sclerosis-prone strain. Because fewer d(CA) repeats associated with decreased MMP-9 expression in MC, it might be a genetic marker for glomerulosclerosis.
Editor: Hagerstown, MD: Lippincott Williams & Wilkins
Idioma: Inglês

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Association of a decreased number of d(CA) repeats in the matrix metalloproteinase-9 promoter with glomerulosclerosis susceptibility in mice

FORNONI, Alessia ; YINGCAI WANG ; LENZ, Oliver ; STRIKER, Liliane J ; STRIKER, Gary E

Hagerstown, MD: Lippincott Williams & Wilkins

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