Involvement of bone marrow-derived endothelial progenitor cells in glomerular capillary repair in habu snake venom-induced glomerulonephritis.
Neovasculogenesis is essential in tissue remodeling. Endothelial progenitor cells (EPCs) mobilize from bone marrow (BM) and participate in neovasculogenesis. This study examined the role of EPCs in a model of reversible glomerulonephritis induced by habu snake venom (HSV). Lethally irradiated FVB/N wild-type mice were transplanted with BM cells from donor transgenic mice expressing beta-galactosidase gene under the control of endothelial-specific tie-2 promoter. HSV or saline was injected intravenously after BM transplantation (BMT). The kidneys were removed before injection and at days 1, 7, 28, and 56 after injection. beta-Galactosidase-expressing cells were identified by X-gal staining. The expressions of CD31 (endothelial cell marker) and vascular endothelial cell growth factor (VEGF) in renal tissues were examined by immunohistochemistry. In BMT mice injected with saline, few X-gal-positive cells were detected in glomeruli. In HSV-injected mice, X-gal-positive EPCs were increased in damaged glomeruli, reaching maximum at day 28. Recovery of glomeruli was observed at day 56 in association with reduction of X-gal-positive EPCs. VEGF overexpression was detected in glomerular epithelial and endothelial cells, mesangial cells, and EPCs. Our results indicated that EPCs were mobilized into the damaged glomeruli, suggesting EPCs participation in glomerular capillary repair of damaged glomeruli in HSV-induced glomerulonephritis.
Division of Nephrology, Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan. yyoshiwo@hotmail.com
Yoko
Y
Abe-Yoshio
Katsushige
K
Abe
Masanobu
M
Miyazaki
Akira
A
Furusu
Tomoya
T
Nishino
Takashi
T
Harada
Takehiko
T
Koji
Shigeru
S
Kohno
D000818:Animals; D016026:Bone Marrow Transplantation; D002196:Capillaries / Q000166:cytology*; D002454:Cell Differentiation; D003435:Crotalid Venoms / Q000009:adverse effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005921:Glomerulonephritis / Q000139:chemically induced / Q000473:pathology*; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D017841:Trimeresurus; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D003435:Crotalid Venoms; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D001616:beta-Galactosidase