The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis.

Tytuł:: The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis.
Autorzy:: Yuan Y; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China.
Fan G; Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China.
Liu Y; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China.
Liu L; Department of Anesthesiology, Weifang Medical University, Weifang, 261000, China.
Zhang T; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China.
Liu P; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China.
Tu Q; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China.
Zhang X; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China.
Luo S; Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Yao L; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China. yao_.
Chen F; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China. .
Li J; Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China. .
Źródło:: Cellular & molecular immunology [Cell Mol Immunol] 2022 Apr; Vol. 19 (4), pp. 504-515. Date of Electronic Publication: 2022 Jan 04.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Beijing, China : Tokyo, Japan : Chinese Society of Immunology; Nature Pub. Group, 2010-
MeSH Terms:: Sepsis*
Transcription Factors*/metabolism
Animals ; Glycolysis ; Hexokinase ; Humans ; Immunity ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL
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Contributed Indexing:: Keywords: Glycolysis; HK2; KLF14; Macrophages; Perhexiline; Sepsis
Substance Nomenclature:: 0 (KLF14 protein, human)
0 (Klf14 protein, mouse)
0 (Kruppel-Like Transcription Factors)
0 (Transcription Factors)
EC 2.7.1.1 (Hexokinase)
EC 2.7.1.1 (hexokinase 2, mouse)
Entry Date(s):: Date Created: 20220105 Date Completed: 20220405 Latest Revision: 20221023
Update Code:: 20240104
PubMed Central ID:: PMC8976055
DOI:: 10.1038/s41423-021-00806-5
PMID:: 34983946
: Czasopismo naukowe

Sepsis is a heterogeneous syndrome induced by a dysregulated host response to infection. Glycolysis plays a role in maintaining the immune function of macrophages, which is crucial for severely septic patients. However, how the pathways that link glycolysis and macrophages are regulated is still largely unknown. Here, we provide evidence to support the function of KLF14, a novel Krüppel-like transcription factor, in the regulation of glycolysis and the immune function of macrophages during sepsis. KLF14 deletion led to significantly increased mortality in lethal models of murine endotoxemia and sepsis. Mechanistically, KLF14 decreased glycolysis and the secretion of inflammatory cytokines by macrophages by inhibiting the transcription of HK2. In addition, we confirmed that the expression of KLF14 was upregulated in septic patients. Furthermore, pharmacological activation of KLF14 conferred protection against sepsis in mice. These findings uncover a key role of KLF14 in modulating the inflammatory signaling pathway and shed light on the development of KLF14-targeted therapeutics for sepsis.
(© 2021. The Author(s).)

Erratum in: Cell Mol Immunol. 2022 Feb 8;:. (PMID: 35136226)

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