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2012 Fiscal Year Final Research Report

Role of Toll-like receptor 4 in kidney-lung crosstalk

Research Project

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Project/Area Number 23790931
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

DOI Kent  東京大学, 医学部附属病院, 講師 (80505892)

Project Period (FY) 2011 – 2012
Keywords腎臓学 / 急性腎障害
Research Abstract

Acute lung injury (ALI) and acute kidney injury (AKI) are severe complications in critically ill patients. These two organ dysfunctions synergistically increase mortality in intensive care units. Organ cross-talk between the kidney and the lung has been suggested recently as amplifying each organ injury. This study was conducted to identify a possible mechanism of AKI-induced ALI using a mouse bilateral nephrectomy (BNx) model. Toll-like receptor 4 (TLR4)-mutant C3He/J mice were resistant to lung injury including neutrophil infiltration and increased neutrophil elastase (NE) activity caused by BNx. High-mobility group protein B1 (HMGB1) is one of the agonists for TLR4. Its blood concentrations were increased significantly by BNx. Blockade of HMGB1 by neutralizing antibody reduced lung injury not in TLR4-mutant C3He/J but in TLR4-wild type C3He/N mice. These data suggest that enhanced HMGB-1-TLR4 pathway contributes to lung injury induced by BNx. Targeting the HMGB-1-TLR4 pathway will enable development of a new therapeutic strategy to improve the outcome of severely ill patients with ALI and AKI.

  • Research Products

    (2 results)

All Other

All Journal Article (1 results) Presentation (1 results)

  • [Journal Article] HMGB-1-TLR4 pathway contributes to acute lung injury induced by bilateral nephrectomy

    • Author(s)
      Kent Doi, Tomoko Ishizu, Emi Ogasawara, Yoshifumi Hamasaki, Naoki Yahagi, Masaomi Nangaku, Eisei Noiri
    • Volume
      (投稿中)
  • [Presentation] Role of Toll-like receptor 4 and HMGB-1 in kidney-lung crosstalk Kent Doi

    • Author(s)
      Kent Doi, Tomoko Ishizu, Emi Ogasawara, Yoshifumi Hamasaki, Naoki Yahagi, Masaomi Nangaku, Eisei Noiri
    • Organizer
      米国腎臓学会2013 年学術集会

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Published: 2014-09-25  

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