2002 Fiscal Year Final Research Report Summary
Effect of fibroblast-specific suicidal-gene against rapidly progressive glomerulonephritis
| Project/Area Number |
13671127
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Saitama Medical School |
|---|
Principal Investigator |
OKADA Hirokazu OKADA,Hirokazu, 医学部, 講師 (60233342)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KANNO Yoshihiko Saitama Medical School, Medicine, Assistant, 医学部, 助手 (30276232)
SUZUKI Hiromichi Saitama Medical School, Medicine, Professor, 医学部, 教授 (80129494)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | Rapidly progressive glomerulo-nephritis / fibrosis / fibroblast / gene therapy |
|---|
| Research Abstract |
The extent of renal fibrosis is the best predictor for functional outcomes in a variety of progressive renal diseases. Interstitial fibroblasts and fibroblast-like cells (FbLCs) are presumably involved In the fibrotic process. However, such FbLCs have never been well-characterized in the kidney. Therefore, in this study, we characterized them using immunohistochemistry and in situ hybridization with phenotypic and functional marker probes. In the interstitium of anti-glomerular basement membrane (αGBM) nephritic kidneys, fibroblast-specific protein1 (FSP1)^+ fibroblasts were demonstrated to produce connective tissue growth factor (CTGF) and type I collagen (COLI) whereas vimentin^+ FbLCs synthesized transforming growth factor-β1. To prove whether FSP1^+ fibroblasts played an essential role in renal fibrogenesis, we employed mice transgenic for a deleted form of thymidine kinase (dTK) cDNA under the control of FSP1 promoter (FSP1.dTK^+). Since the transgenic FSP1^+ fibroblasts were dual-positive for TK protein, and these proliferating cells went apoptosis when gancyclovir (GCV) was administered, we generated αGBM nephritis in them and treated them with GCV. In the αGBM nephritic kidney of these FSP1.dTK^+ mice, GCV treatment significantly suppressed the increase in the number of FSP1^+ fibroblasts and the production of CTGF and COLI, resulting in the attenuation of renal fibrogenesis successfully. FSP1^+ were demonstrated to be a master contributor in the fibrosing kidneys, and the FSP1 gene-guided anti-fibrotic therapies seem promising for a variety of progressive renal diseases.
|
