title: Angiopoietin 1 and 2 gene and protein expression is differentially regulated in acute anti-Thy1.1 glomerulonephritis.
abstract: Capillary neoformation is important in repair of glomerular injury of various origins. VEGF was shown to be crucial for glomerular capillary repair in glomerulonephritis (GN). We reasoned that other angiogenic factors are likewise involved in glomerular capillary remodeling and found angiopoietin 1 and -2 (ANG1 and ANG2) mRNA to be upregulated in cDNA microarrays of microdissected glomeruli of anti-Thy1.1 GN of the rat. We then studied glomerular in situ gene and protein expression of ANG1 and ANG2 and their receptor Tie-2 in the course of anti-Thy1.1 GN, which was induced by injection of OX-7 antibody. Animals were perfusion fixed at days 6 and 12 after GN induction and compared with nonnephritic controls receiving PBS. Capillary damage and repair were quantitatively analyzed using stereological techniques. Gene and protein expression of ANG1 and ANG2 and their receptor Tie-2 was analyzed using real-time quantitative PCR from microdissected glomeruli, nonradioactive in situ hybridization, double immunofluorescence, and Western blot analysis. Glomerular capillarization assessed as length density was significantly lower at day 6 of anti-Thy1.1 GN than in controls; it was back to normal values at day 12. ANG1 and ANG2 gene expression was markedly upregulated at day 6 of the disease compared with controls. Protein expression of ANG1 and ANG2 was confined to podocytes and that of Tie-2 to endothelial cells. At day 12 of anti-Thy1.1 GN when capillary restoration was nearly completed, ANG1 and ANG2 gene expression returned to basal levels, whereas Tie-2 expression was still high. With the use of a combined molecular and in situ approach, the spatial and temporal gene and protein expression of the angiopoietins and their receptor was analyzed in anti-Thy1.1 GN. The results indicate that glomerular expression of ANG1 and ANG2 and Tie-2 is differentially regulated and may contribute to healing and endothelial cell stabilization in experimental GN.
authors.affiliation: Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr. 12, 91054 Erlangen, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Câmpean
authors.forename: Britta
authors.initials: B
authors.lastname: Karpe
authors.forename: Christian
authors.initials: C
authors.lastname: Haas
authors.forename: Akram
authors.initials: A
authors.lastname: Atalla
authors.forename: Harm
authors.initials: H
authors.lastname: Peters
authors.forename: Harald
authors.initials: H
authors.lastname: Rupprecht
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebner
authors.forename: Till
authors.initials: T
authors.lastname: Acker
authors.forename: Karl
authors.initials: K
authors.lastname: Plate
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
mesh_terms: D000208:Acute Disease; D042683:Angiopoietin-1 / Q000096:biosynthesis / Q000235:genetics*; D042702:Angiopoietin-2 / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D002196:Capillaries / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D005921:Glomerulonephritis / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000473:pathology; D007834:Lasers; D042282:Microdissection; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D042787:Receptor, TIE-2 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018800:Thy-1 Antigens; D042461:Vascular Endothelial Growth Factor A; D012313:RNA; D042787:Receptor, TIE-2