1996 Fiscal Year Final Research Report Summary
Role of DNA binding protein for occurrence of the glomerulosclerosis with aging
| Project/Area Number |
07671258
|
|---|
| 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 |
NAGASAWA Ryuji Saitama Medical School, Medicine, Associate Professor, 医学部, 講師 (70146794)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Naoki Tokyo Metropolitan Institute of Gerontology, Molecular Pathology, Head, 分子病理部内, 部長 (00115940)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Keywords | DNA binding protein / c-fos / glomerulosclerosis / aging / proto-oncogene |
|---|
| Research Abstract |
Gene expression is regulated by DNA binding proteins which bind to the promoter/enhancer element of the responsible gene. One such protein is known as activator protein-1 (AP-1). AP-1 has been identified as the transcriptional product of several of the jun and fos proto-oncogene families. Fos and Jun associate each other to generate stable heterodimers which have high DNA binding activity. We have previously found that the expression of c-fos and c-jun increases with aging in rat kidneys. The main pathological features with aged rat kidney is focal glomerulosclerosis with accumulation of various extracellular matrix. This pathological change could be due to the age related increase of c-fos and c-jun products. The aim of the present study was to clarify the role of c-fos gene for the development of age associated glomerulosclerosis. For this purpose, two mesangial cell lines were established : One is a rat mesangial cell line transfected with c-fos gene, and the other is that derived from c-fos transgenic mouse. When these cell lines were cultured in low glucose (10mM) condition, confocal microscopic analysis revealed that the expression of Fos exceeds to that of control cells under high glucose (30mM) condition. Level of laminin B1 mRNA was elevated in c-fos overexpressed mesangial cells even in low glucose condition. These results indicated that some kind of extracellular matrix are under the control of Fos, and that the age related increase of extracellular matrix in the sclerotic kidney may partly be due to the age associate increase of Fos.
|
