| Project/Area Number |
16390247
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
KURIHARA Hidetake Juntendo Univ School of Med, Associate Professor, 医学部, 准教授 (80311976)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKAI Tatsuo Juntendo Univ School of Med, Professor, 医学部, 教授 (90114488)
ICHIMURA Koichiro Juntendo Univ School of Med, Assistant Professor, 医学部, 助教 (10343485)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
|
|---|
| Keywords | Glomerulus / Podocyte / Proteinuria / Cell Culture / Slit membrane / PCR / Nephrosis |
|---|
| Research Abstract |
Glomerular podocyte is a terminally differentiated cell and its disorder influences glomerular filtration immediately, and causes albuminuria. Using a novel congenital nephrotic rat and immortalized rat podocyte cell lines, we clarify the causative proteins on nephrosis and examine the regulatory mechanism of their expression in this study. Results obtained are described below. 1) We examined the pathophysiology of newly established congenital nephrotic (NPS) rat kidney. Podocytes are selectively injured in NPS rat glomeruli. Then, mRNA expression of podocyte-specific genes on the microdissected glomeruli from superficial and juxtamedullary areas were analyzed by using RT-PCR. Nephrin and NEPH-1 were reduced in the superficial glomeruli when compared with the juxtamedullary ones. Immunocytochemical analysis also demonstrated that slit diaphragm-related molecules (nephrin and podocin) were selectively decreased in the superficial glomeruli. The dramatic decrease of slit-diaphargm-relate
… More
d molecues is tightly related with the reverse of podocyte cell growth. 2) It found that the -snail molecule causing the epithelial-mesenchymal transformation induces the downregulation of nephrin. 3) We found that SIRP-alpha, which recruits SHP to the membrane, is expressed at the base of slit diaphragm and the basal membrane in podocyte and regulates tyrosine phosphorylation of molecules. Moreover, CD47, a ligand of SIRP-alpha, was expressed in the mesangial cell and the endothelial cell, suggesting that the molecular interaction between SIRP-alpha and CD47 is important for the cellular communication in glomerulus. 4) We found that the direct interaction between nephrin and MAGI-1, which is a scaffolding protein localized at the tight junction. The new molecule LNX, a binding partner of JAM4, is found and its functional role is clarified. 5) Foot process formation was analyzed by using the established podocyte cell lines. We found that the depolymerization of actin filament followed by reconstruction of microtubles and intermediate filaments induced by elevation of cAMP triggers cellular projection formation. Less
|
