title: Transforming growth factor β-induced protein promotes severe vascular inflammatory responses.
abstract: BACKGROUND
  Sepsis is a systemic inflammatory condition resulting from bacterial infections; it has a high mortality rate and limited therapeutic options. Despite extensive research into the mechanisms driving bacterial sepsis, the target molecules controlling vascular leakage are still largely unknown. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types, which is known to interact with integrins.
  
  
  OBJECTIVE
  The aim of this study was to determine the roles of TGFBIp in vascular proinflammatory responses, and the mechanisms of action driving these responses.
  
  
  METHODS
  Circulating levels of TGFBIp were measured in patients admitted to the hospital with sepsis, severe sepsis, and septic shock and in cecal ligation and puncture (CLP)-induced septic mice. Effects of TGFBIp knockout on CLP-induced septic mortality and effects of TGFBIp on multiple vascular proinflammatory responses were determined.
  
  
  RESULTS
  Circulating levels of TGFBIp were significantly elevated compared with healthy controls, and were strongly correlated with disease severity. High blood TGFBIp levels were also observed in CLP-induced septic mice. The absence of the TGFBIp gene in mice attenuated CLP-induced sepsis. TGFBIp enhanced vascular proinflammatory responses including vascular permeability, adhesion and migration of leukocytes, and disruption of adherence junctions through interacting with integrin αvβ5.
  
  
  CONCLUSIONS
  Collectively, our findings demonstrate that the TGFBIp-αvβ5 axis can elicit severe inflammatory responses, suggesting it to be a potential target for development of diagnostics and therapeutics for sepsis.
authors: 1 College of Pharmacy, Research Institute of Pharmaceutical Sciences.
authors: Jong-Sup
authors: JS
authors: Bae
authors: Wonhwa
authors: W
authors: Lee
authors: Ju-Ock
authors: JO
authors: Nam
authors: Jung-Eun
authors: JE
authors: Kim
authors: Shin-Woo
authors: SW
authors: Kim
authors: In-San
authors: IS
authors: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002432:Cecum / Q000601:surgery; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D016326:Extracellular Matrix Proteins / Q000097:blood*; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D019030:Receptors, Vitronectin / Q000097:blood; D018805:Sepsis / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000097:blood*; D000099222:betaIG-H3 Protein
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D019030:Receptors, Vitronectin; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C064660:integrin alphaVbeta5