NNMT/1-MNA protects against hepatic ischemia-reperfusion injury through the AKT/FOXO1/ANGPT2/JNK axis

Bing Yin, Baolin Qian, Hongjun Yu, Shanjia Ke, Zihao Li, Yongliang Hua, Shounan Lu, Chaoqun Wang, Mengxin Li, Sixun Guo, Zhongyu Li, Yongzhi Zhou, Zhanzhi Meng, Xinglong Li, Yanan Xu, Zhigang Feng, Miaoyu Bai, Yao Fu, Wei Tang, Shangyu Hong () and Yong Ma ()
Additional contact information
Bing Yin: The First Affiliated Hospital of Harbin Medical University
Baolin Qian: The First Affiliated Hospital of Harbin Medical University
Hongjun Yu: The First Affiliated Hospital of Harbin Medical University
Shanjia Ke: The First Affiliated Hospital of Harbin Medical University
Zihao Li: The First Affiliated Hospital of Harbin Medical University
Yongliang Hua: Ministry of Education
Shounan Lu: The First Affiliated Hospital of Harbin Medical University
Chaoqun Wang: The First Affiliated Hospital of Harbin Medical University
Mengxin Li: Fudan University
Sixun Guo: The First affiliated Hospital of Harbin Medical University
Zhongyu Li: The First Affiliated Hospital of Harbin Medical University
Yongzhi Zhou: The First Affiliated Hospital of Harbin Medical University
Zhanzhi Meng: The First Affiliated Hospital of Harbin Medical University
Xinglong Li: The First Affiliated Hospital of Harbin Medical University
Yanan Xu: Ministry of Education
Zhigang Feng: Ministry of Education
Miaoyu Bai: The First Affiliated Hospital of Harbin Medical University
Yao Fu: The First Affiliated Hospital of Harbin Medical University
Wei Tang: National Center for Global Health and Medicine
Shangyu Hong: The First Affiliated Hospital of Harbin Medical University
Yong Ma: The First Affiliated Hospital of Harbin Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Hepatic ischemia‒reperfusion injury (HIRI) occurs during liver surgery, contributing to postoperative complications such as liver failure, prolonged hospital stays, and increased morbidity and mortality rates. Yet, the mechanism underlying HIRI remains unclear. Nicotinamide N-methyltransferase (NNMT) facilitates the conversion of nicotinamide into N1-methylnicotinamide (1-MNA) and plays crucial roles in various pathophysiological processes. In this study, we find a decrease in hepatic NNMT expression and serum 1-MNA levels during HIRI. Both NNMT overexpression and exogenous 1-MNA treatment alleviate HIRI in male mice HIRI models and primary hepatocytes H/R models. Mechanistically, NNMT/1-MNA plays key roles in inflammation, apoptosis, and vascular injury during HIRI through the AKT/FOXO1/ANGPT2/JNK axis. Hepatic-specific depletion of NNMT leads to increased ANGPT2 expression and exacerbates HIRI, effects that can be mitigated by ANGPT2 knockdown. Our findings suggest that NNMT/1-MNA/ANGPT2 may regulate HIRI via the JNK signaling pathway. In summary, we present the function of NNMT and its underlying mechanism in liver injury, providing potential new therapeutical strategies for addressing HIRI.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59968-9 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:16:y:2025:i:1:d:10.1038_s41467-025-59968-9

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

DOI: 10.1038/s41467-025-59968-9

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 ().