PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis

Liangchun Yang, Min Xie, Minghua Yang, Yan Yu, Shan Zhu, Wen Hou, Rui Kang, Michael T. Lotze, Timothy R. Billiar, Haichao Wang, Lizhi Cao () and Daolin Tang ()
Additional contact information
Liangchun Yang: Xiangya Hospital, Central South University
Min Xie: Xiangya Hospital, Central South University
Minghua Yang: Xiangya Hospital, Central South University
Yan Yu: Xiangya Hospital, Central South University
Shan Zhu: Xiangya Hospital, Central South University
Wen Hou: University of Pittsburgh
Rui Kang: University of Pittsburgh
Michael T. Lotze: University of Pittsburgh
Timothy R. Billiar: University of Pittsburgh
Haichao Wang: Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research
Lizhi Cao: Xiangya Hospital, Central South University
Daolin Tang: University of Pittsburgh

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: Abstract Increasing evidence suggests the important role of metabolic reprogramming in the regulation of the innate inflammatory response, but the underlying mechanism remains unclear. Here we provide evidence to support a novel role for the pyruvate kinase M2 (PKM2)-mediated Warburg effect, namely aerobic glycolysis, in the regulation of high-mobility group box 1 (HMGB1) release. PKM2 interacts with hypoxia-inducible factor 1α (HIF1α) and activates the HIF-1α-dependent transcription of enzymes necessary for aerobic glycolysis in macrophages. Knockdown of PKM2, HIF1α and glycolysis-related genes uniformly decreases lactate production and HMGB1 release. Similarly, a potential PKM2 inhibitor, shikonin, reduces serum lactate and HMGB1 levels, and protects mice from lethal endotoxemia and sepsis. Collectively, these findings shed light on a novel mechanism for metabolic control of inflammation by regulating HMGB1 release and highlight the importance of targeting aerobic glycolysis in the treatment of sepsis and other inflammatory diseases.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/ncomms5436 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5436

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms5436

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().