2000 Fiscal Year Final Research Report Summary
The Role of Angiogenesis in the Progression of Tubulointerstitial Injury in the Scarred Kidney Secondary to Urinary Tract Diseases
| Project/Area Number |
10470328
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
SAKAI Kiyohide Tohuku University School of Medicine, Department of Urology, Research Associate, 大学院・医学系研究科, 助手 (00271908)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KONDA Ryuichiro Tohuku University School of Medicine, Department of Urology, Associate Professor, 医学部・附属病院, 講師 (10225609)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Keywords | kidney / renal function / fibrosis / angiogenesis / Platelet-derived endothelial cell growth factor / Interleukin-6 / Vascular endothelial growth factor / reflux nephropathy / obstructive uropathy |
|---|
| Research Abstract |
In chronic inflammation, tumor growth and wound healing, hypoxia and/or inflammatory cell infiltration appear to be the common events preceding neovascularization. Tubulointerstital pathology characterized by tubular atrophy, interstitial fibrosis and mononuclear cell infiltration is primary lesion of the scarred kidneys secondary to variety of urinary tract diseases and causes local ischemia via obliteration of the postglomerular capillary network. Although angiogenesis is assumed to be upregulated in the scarred kidneys, we have little information concerning new vessel formation secondary to tubulointerstitial injury. We examined microvessel count in the scarred kidneys and elucidated that number of microvessel increased with increasing interstitial fibrosis. The expression of platelet-derived endothelial cell growth factor (PD-ECGF), one of potent stimulators for angiogenesis, increased in the tubular epithelial cells and mononuclear infiltrates located in the areas with interstitial fiborsis. A significant correlation was found between microvessel count and the degree of interstitial fibrosis or the expression of PD-ECGF.
Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that promotes angiogenesis. We determined levels of urinary VEGF in the patients with reflux nephropathy. Urinary VEGF levels were significantly higher in the patients with severe renal scarring compared with normal controls or those with mild renal scarring. Immunohistochemical examination of VEGF showed an increased expression of this protein in the tubular epithelial cells in and adjacent to fibrotic areas where microvessel count increased. We suggest from these observations that an increase of urinary VEGF value may reflect the up-regulation of this protein.
We suggest from these observations that angiogenesis may play a critical role in the progression of tubulointerstitial injury.
|
