Glucocorticoid ameliorates altered gene expression of extracellular matrix components in kidneys of New Zealand black/white F1 mice.
1. We examined the effects of methylprednisolone on the levels of messenger RNA encoding for extracellular matrix components, including alpha 1(IV) collagen chain, laminin B1 and B2 chains, heparan sulphate proteoglycan and alpha 1(I) and alpha 1(III) collagen chains, and on the accumulation of these proteins in the renal cortex of New Zealand Black/White F1 mice. 2. At the onset of nephritis, at about 5 months of age, New Zealand Black/White F1 mice were divided in two groups that received either methylprednisolone or saline injections for 5 months. 3. The development of histological lesions and the glomerular deposition of IgG, IgM and C3 were suppressed by methylprednisolone treatment from 5 to 10 months of age. 4. The distribution and intensity of type IV collagen, laminin, heparan sulphate proteoglycan, type I collagen and type III collagen in renal cortex were decreased by the administration of methylprednisolone. 5. Levels of messenger RNA encoding for alpha 1(IV) collagen chain, laminin B1 and B2 chains, heparan sulphate proteoglycan and alpha 1(I) and alpha 1(III) collagen chains in the renal cortex of New Zealand Black/White F1 mice were significantly ameliorated at 8-10 months of age by methylprednisolone administration. 6. These results indicate that methylprednisolone treatment can serve as an effective therapeutic approach to abnormal extracellular matrix regulation in murine lupus nephritis.
Nakamura
T
T
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Ebihara
I
I
Tomino
Y
Y
Koide
H
H
D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007668:Kidney / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism; D008181:Lupus Nephritis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D008775:Methylprednisolone / Q000627:therapeutic use*; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000209:etiology; D012333:RNA, Messenger / Q000096:biosynthesis*; D013997:Time Factors
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D003094:Collagen; D008775:Methylprednisolone