한빛사 논문
Jong-Sup Bae1,2#,*, Wonhwa Lee1,2,#, Ju-Ock Nam3, Jung-Eun Kim4, Shin-Woo Kim5 and In-San Kim2,6,*
1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea; 2Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea; 3Department of Ecological Environment Conservation, Kyungpook National University, Sangju-si, Gyeongsangbuk-do 742-170, Republic of Korea; 4Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422, Korea; 5Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea; 6Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 136-791, Republic of Korea;
#Two authors contributed equally to this work.
* Corresponding Authors; Jong-Sup Bae, In-San Kim
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 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 and Results: Circulating levels of TGFBIp were measured in patients admitted to the intensive care unit with sepsis, severe sepsis, and septic shock; levels of this protein were significantly elevated compared with healthy controls, and were strongly correlated with disease severity. High blood TGFBIp levels were also observed in cecal ligation and puncture (CLP)-induced septic mice. The absence of the TGFBIp gene in mice attenuated CLP-induced sepsis. TGFBIp enhanced multiple 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.
KEYWORDS: TGFBIp, sepsis, endothelial dysfunction, permeability, CLP
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