FUNCTIONAL ANALYSIS OF THE FULL-LENGTH ERYTHROPOIETIN RECEPTOR EXPRESSED IN ACQUIRED CYSTIC DISEASE OF THE KIDNEY
| Project/Area Number |
13671658
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | 大分医科大学 |
|---|
Principal Investigator |
NOMURA Yoshio OITA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF ONCOLOGICAL SCIENCE (UROLOGY), PROFESSOR, 医学部, 教授 (90040550)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIMATA Hiromitu OITA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF ONCOLOGICAL SCIENCE (UROLOGY), ASSOCIATE PROFESSOR, 医学部, 助教授 (60219714)
SATO Fuminori OITA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF ONCOLOGICAL SCIENCE (UROLOGY), INSTRUCTOR (30305049)
黒光 浩一 大分医科大学, 医学部, 助手 (80305052)
|
|---|
| Project Period (FY) |
2001 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | ERYTHROPOIETIN / ERYTHROPOIETLN RECEPTOR / KIDNEY / ACQUIRED CYSTIC DISEASE OF THE KIDNEY / APOPTOSIS / CYST FORMATION / SIGNAL TRANSDUCTION / 多嚢胞化萎縮腎 / IκB / NFκB |
|---|
| Research Abstract |
PURPOSE : We investigated the expression of EPO and EPO-receptor (EPO-R) in ACDK and furthermore examined the relationship of those exression with the proliferation and apoptosis of tubular cells in ACDK.
MATERIALS AND METHODS : 13, kidney specimens were obtained from 12 patients on long-term hemodialysis. Immunohistochemical study was performed with anti-EPO, anti-EPO-R, anti-Bcl-2 and anti-Ki-67 antibodies. Tubular proliferation was examined by Ki-67 labeling index. Total RNAs were extracted from frozen kidney specimens. Expressions of EPO and EPO-R mRNAs were detected by RT-PCR. Effects of EPO on the proliferation and intracellular signal transduction of primary human proximal tubular cells (HPTC) were examined by WST-1 assay and immunoblot assay.
RESULTS : Immunohistochemical study revealed that EPO was detected in all epithelial cells of the cysts, tubular cells and peri-tubular cells. In contrast, positive staining of EPO-R was only observed in epithelial cells of the cysts and tubular cells. mRNAs of EPO and EPO-R were also detected in the cystic epithelium. Ki-67 labeling indices of epithelial cells of the cysts, tubular cells and peri-tubular cells were 9.6%, 6.7% and 0%, respectively. PCR direct sequence demonstrated the presence of full-length EPO-R which has functional domain in the cytoplasmic region. EPO increased the proliferation of HPTC by dose-dependent fashion, but it did not increased the phosphorylation of I κ B nor STAT5 proteins.
CONCLUSION : EPO and functional EPO-R were co-expressed in tubular cells and epithelial cells of the cysts in ACDK. EPO and EPO-R may be involoved in the proliferation and cyst formation in long-term hemodialysis kidney by autocrine and/or paracrine mechanism.
|
Report
(4 results)
Research Products
(1 results)
