Transforming Growth Factor beta-induced Protein Promotes Severe Vascular Inflammatory Responses

Authors
Bae, Jong-SupLee, WonhwaNam, Ju-OckKim, Jung-EunKim, Shin-WooKim, In-San
Issue Date
2014-04
Publisher
AMER THORACIC SOC
Citation
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, v.189, no.7, pp.779 - 786
Abstract
Rationale: 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 beta-induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types, which is known to interact with integrins. Objectives: 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. Measurements and Main 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 alpha v beta 5. Conclusions: Collectively, our findings demonstrate that the TGFBIp-alpha v beta 5 axis can elicit severe inflammatory responses, suggesting it to be a potential target for development of diagnostics and therapeutics for sepsis.
Keywords
ENDOTHELIAL BARRIER FUNCTION; ORGAN DYSFUNCTION SYNDROME; INTEGRIN ALPHA-V-BETA-5; SEVERE SEPSIS; ADHESION MOLECULE; SEPTIC SHOCK; BETA-IG-H3; PERMEABILITY; BIOMARKERS; MIGRATION; transforming growth factor beta-induced protein; sepsis; endothelial dysfunction; permeability; cecal ligation and puncture
ISSN
1073-449X
URI
https://pubs.kist.re.kr/handle/201004/126899
DOI
10.1164/rccm.201311-2033OC
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KIST Article > 2014
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