title: Angiopoietins modulate endothelial adaptation, glomerular and podocyte hypertrophy after uninephrectomy.
abstract: Glomerular capillary remodeling is an essential process in the development of glomerular hypertrophy. Angiopoietins, which are important regulators in angiogenesis, plays a role in the development of glomerulus during embryogenesis. Here, we evaluated the influence of angiopoietin on glomerular components and hypertrophy after uninephrectomy in adult male BALB/c mice. The actions of angiopoietin 1 or 2 were systemically antagonized by the subcutaneous administration of antagonists. We observed that the angiopoietin system was activated after uninephrectomy, and that the blockade of angiopoietin 1 or 2 decreased the activation of the angiopoietin receptor--tyrosine kinase with Ig and EGF homology domains-2--and attenuated the development of glomerular and podocyte hypertrophy. The increase in endothelial density staining (anti-CD31) following uninephrectomy was also reversed by angiopoietin 1 or 2 blockades. Glomerular basement thickness and foot process width were observed to decrease in the angiopoietin blockade groups. These changes were associated with the down regulation of the expression of genes for the glomerular matrix and basement membrane, including collagen type IV α1, collagen type IV α2, collagen type IV α5, and laminin α5. Thus, angiopoietin 1 or 2 may play an important role in the development of glomerular hypertrophy after uninephrectomy. A blockade of the angiopoietin system not only influenced the endothelium but also the podocyte, leading to diminished gene expression and morphological changes after uninephrectomy.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wen Chih
authors.initials: WC
authors.lastname: Chiang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun Fu
authors.initials: CF
authors.lastname: Lai
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan.
authors.forename: Chi Ting
authors.initials: CT
authors.lastname: Su
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei Hao
authors.initials: WH
authors.lastname: Peng
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ching Fang
authors.initials: CF
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Zhudong Branch, Hsinchu County, Taiwan.
authors.forename: Fan Chi
authors.initials: FC
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, E-Da Hospital, Kaohsiung City, Taiwan.
authors.forename: Yi Ting
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan ; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shuei Liong
authors.initials: SL
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yung Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kwan Dun
authors.initials: KD
authors.lastname: Wu
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuo Shyan
authors.initials: KS
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Tun Jun
authors.initials: TJ
authors.lastname: Tsai
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D006984:Hypertrophy / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009392:Nephrectomy; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D042683:Angiopoietin-1; D042682:Angiopoietins; C467628:Angpt1 protein, mouse