title: A novel role of angiopoietin-like-3 associated with podocyte injury.
abstract: BACKGROUND
  Angiopoietin-like-3 (ANGPTL3) expression is increased in glomerular podocytes of nephrotic syndrome. We hypothesize whether ANGPTL3 plays an important role in podocyte injury and promoting proteinuria.
  
  
  METHODS
  Angptl3(+/+) and Angptl3(-/-) female mice on B6;129S5 gene background were injected with adriamycin by tail vein at the dose of 25 mg/Kg to produce nephropathy. Proteinuira was measured and podocytes ultrastructure was observed by electron microscopy. The interaction between ANGPTL3 and intergrin β3 was analyzed by CO-IP and confocal immunofluorescence. The relative gene and protein expression were analyzed by RT-PCR and western blot.
  
  
  RESULTS
  The deletion of ANGPTL3 tremendously attenuates proteinuria (more than a fivefold decrease in albuminuria) and protects podocytes from injury in a mouse model of adriamycin-induced nephropathy. We further demonstrate that ANGPTL3 interacts with and activates podocyte-expressed integrin β3 and regulate expression of α-actinin-4, which may result in the cytoskeletal rearrangement of podocytes. Additionally, we identify the activation of the ANGPTL3-integrin β3 signaling pathway in patients with nephrotic syndrome.
  
  
  CONCLUSIONS
  ANGPTL3 might play a crucial role in podocyte injury. Either decreasing ANGPTL3 expression or interfering with the ANGPTL3-integrin β3 interaction might be benefit for podocyte protection and decrease proteinuira.
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Institute of Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Rao
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Haimei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zha
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Muyi
authors.initials: M
authors.lastname: Guo
authors.affiliation: Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Ruixi
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
mesh_terms: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D004317:Doxorubicin / Q000009:adverse effects; D005260:Female; D039661:Integrin beta3 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D039661:Integrin beta3; D004317:Doxorubicin