1998 Fiscal Year Final Research Report Summary
Pathological Analysis of Expression of Extracellular Matrix in Glomerulonephritis
| Project/Area Number |
09670192
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Nagasaki University |
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Principal Investigator |
RAZZAQUE Mohammed Shawkat Nagasaki University School of Medicine, Assistant, 医学部, 助手 (50264213)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Glomerulonephritis / collagen / heat shock protein 47 / fibrosis / glomerulosclerosis / Pulmonary fibrosis / Extracellular matrix / Renal biopsy |
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| Research Abstract |
To explore the possible role of heat shock protein (HSP) 47 in the process of sclerosis/fibrosis of renal and pulmonary tissue, molecular pathological analysis was performed using experimental animal models and human tissues.
In the experiments of senile model (Fischer 344 rat) and gentamicin-induced renal injury, the expression of HSP was increased in sclerotic glomeruli and fibrotic interstitium. Double immunostaining revealed co-expression of HSP47 and alpha-smooth muscle actin/vimentin. It is suggested that HSP47 may be produced by phenotypically changed cells in these models. In human renal biopsy tissue of diabetic nephropathy and IgA nephropathy, accumulation of collagen type III and collagen type IV was associated with increased expression of HSP47. This is the first study concerning the expression of HSP47 in human renal diseases. Using renal biopsy specimens of human mesangial proliferative glomerulonephritis, collagen type VI was shown to present in the glomerulus, and to increase in amount in proliferative and sclerotic regions. in situ hybridization revealed glomerular epithelial cells may produce collagen type VI in the conditions. By immunohistochemical study of human fibrotic lung diseases, colocalization of collagen and HSP47 was noted in fibrotic lesions.
From these results, it is concluded that overexpression of HSP47 may play an important role in the excessive assembly/synthesis of collagens and can thereby contribute to sclerosis/fibrosis in chronic glomerular disease and pulmonary fibrotic diseases.
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