title: Increased renal angiopoietin-1 expression in folic acid-induced nephrotoxicity in mice.
abstract: Growth factors affect epithelial regeneration after acute renal injury, but less is known regarding the expression of vascular growth factors in this setting. A mouse model of folic acid (FA)-induced nephrotoxicity was used to study the expression of angiopoietins (Ang), factors that bind the Tie-2 receptor and modulate endothelial growth. Tubular damage was detected 1 d after FA administration; in the next 14 d, most tubules regenerated but patchy atrophy, with interstitial fibrosis, was also observed. Ang-1 immunostaining was detected between cortical tubules and in the vasa rectae of vehicle-treated animals. FA-induced nephropathy was associated with the acquisition of Ang-1 immunostaining in renal arterial walls and in a subset of injured cortical tubules that failed to stain with periodic acid-Schiff stain, which indicated that they were distal tubules. Renal Ang-1 protein levels were significantly increased after FA administration, compared with time-matched control values, as assessed by Western blotting. Capillaries between regenerating tubules expressed both Tie-2 and platelet-endothelial cell adhesion molecule. A subset of these endothelia expressed proliferating cell nuclear antigen, whereas capillary proliferation was absent in control samples. Therefore, FA-induced nephropathy is associated with increased Ang-1 protein expression in renal epithelia and arteries. In addition, Tie-2-expressing capillaries near damaged cortical tubules undergo proliferation. Further experiments are required to establish whether these events are functionally related.
authors.affiliation: *Nephro-Urology Unit, Institute of Child Health, University College London, London, United Kingdom; and Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: David A
authors.initials: DA
authors.lastname: Long
authors.affiliation: *Nephro-Urology Unit, Institute of Child Health, University College London, London, United Kingdom; and Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Woolf
authors.affiliation: *Nephro-Urology Unit, Institute of Child Health, University College London, London, United Kingdom; and Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.affiliation: *Nephro-Urology Unit, Institute of Child Health, University College London, London, United Kingdom; and Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Hai T
authors.initials: HT
authors.lastname: Yuan
mesh_terms: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D015153:Blotting, Western; D005492:Folic Acid / Q000506:poisoning*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D042787:Receptor, TIE-2
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; C105373:MEN1 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D011518:Proto-Oncogene Proteins; D005492:Folic Acid; D042787:Receptor, TIE-2