. 2025 May 22;16(1):4779.

doi: 10.1038/s41467-025-59968-9.

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

Bing Yin^#^{1

2}, Baolin Qian^#^{1

2}, Hongjun Yu^#^{1

2}, Shanjia Ke^#^{1

2}, Zihao Li^{1

2}, Yongliang Hua^{2

3}, Shounan Lu^{1

2}, Chaoqun Wang^{1

2}, Mengxin Li⁴, Sixun Guo⁵, Zhongyu Li^{1

2}, Yongzhi Zhou^{1

2}, Zhanzhi Meng^{1

2}, Xinglong Li^{1

2}, Yanan Xu^{2

6}, Zhigang Feng^{2

7}, Miaoyu Bai^{1

2}, Yao Fu⁸, Wei Tang^{9

10}, Shangyu Hong^{11

12}, Yong Ma^{13

14}

Affiliations

¹ Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, China.
³ Department of Pediatric Surgery, the Sixth Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
⁵ Department of Pharmacy, The First affiliated Hospital of Harbin Medical University, Harbin, China.
⁶ Department of Hepatopancreatobiliary Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁷ The First Department of General Surgery, The Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, China.
⁸ Department of Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁹ International Health Care Center, National Center for Global Health and Medicine, Tokyo, Japan.
¹⁰ Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo Hospital, Tokyo, Japan.
¹¹ Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. shangyu_hong@fudan.edu.cn.
¹² State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. shangyu_hong@fudan.edu.cn.
¹³ Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. mayong@ems.hrbmu.edu.cn.
¹⁴ Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, China. mayong@ems.hrbmu.edu.cn.

^# Contributed equally.

PMID: 40404636
PMCID: PMC12098763
DOI: 10.1038/s41467-025-59968-9

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

Bing Yin et al. Nat Commun. 2025.

. 2025 May 22;16(1):4779.

doi: 10.1038/s41467-025-59968-9.

Authors

Affiliations

¹ Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, China.
³ Department of Pediatric Surgery, the Sixth Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
⁵ Department of Pharmacy, The First affiliated Hospital of Harbin Medical University, Harbin, China.
⁶ Department of Hepatopancreatobiliary Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁷ The First Department of General Surgery, The Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, China.
⁸ Department of Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁹ International Health Care Center, National Center for Global Health and Medicine, Tokyo, Japan.
¹⁰ Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo Hospital, Tokyo, Japan.
¹¹ Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. shangyu_hong@fudan.edu.cn.
¹² State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. shangyu_hong@fudan.edu.cn.
¹³ Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. mayong@ems.hrbmu.edu.cn.
¹⁴ Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, China. mayong@ems.hrbmu.edu.cn.

^# Contributed equally.

PMID: 40404636
PMCID: PMC12098763
DOI: 10.1038/s41467-025-59968-9

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

**Fig. 1. The expression of NNMT and the levels of 1-MNA decreased after HIRI.**
A The clinical liver specimens obtained from patients undergoing partial hepatectomy. B, C The expression level of NNMT in clinical samples (n = 5, P = 0.003425). D The serum concentration of 1-MNA in patients with partial hepatectomy. E Illustration of the experimental procedures (n = 5, P = 0.01708). F–H The mRNA and protein levels of NNMT in a mouse HIRI model (F: n = 5, P = 0.000044, 0.000043, 0.006934, 0.109756, 0.00032; H: n = 5. P = 0.000232, 0.000201, 0.00061, 0.002913, 0.002433). I The immunohistochemical staining of NNMT in the livers (scale bar: 100 μm). J The serum concentration of 1-MNA in a mouse HIRI model (n = 5, P = 0.00521). K, L The expression level of NNMT in a mouse primary hepatocyte model of H/R (n = 3, P = 0.001734). The results are expressed as mean ± SD. Three biologically independent experiments. Source data are provided as a Source data file. Figure 1A,E were created in BioRender. Bing, Y. (2025) https://BioRender.com/vesbjfg. H/R Hypoxia and reoxygenation, IHC immunohistochemistry, IR ischemia reperfusion, 1-MNA N¹-methylnicotinamide, NNMT Nicotinamide N-methyltransferase, IHC immunohistochemistry, Pre preoperative, Post postoperative.

**Fig. 2. NNMT protected against H/R-induced inflammation and apoptosis.**
A The CCK-8 assay in primary hepatocytes indicating cell viability (n = 3, P = 0.001145, 0.000417). B The LDH levels indicating cell death (n = 3, P = 0.000022, 0.005097). C The mRNA levels of IL-6, TNF-α and MIP-2 in primary hepatocytes (n = 3, P = 0.000794, 0.001265, 0.000059, 0.022793, 0.000491, 0.011172, 0.000029, 0.004128). D–F The cell viability, LDH levels, and mRNA expression of inflammatory cytokines in primary hepatocytes infected with *Nnmt* knockdown virus (D: n = 3, P = 0.001539, 0.001623; E: n = 3, P = 0.0000004, 0.000142; F: n = 3, P = 0.000001, 0.001327, 0.000022, 0.008395, 0.005692, 0.006005, 0.000007, 0.016065). G–J The NF-κB signaling pathway in primary hepatocytes (H: n = 3, P = 0.002815, 0.017879, 0.003711, 0.038824, 0.001359, 0.000751, 0.000044, 0.000163; J: n = 3, P = 0.000008, 0.033984, 0.000105, 0.012657, 0.003946, 0.028127, 0.000152, 0.000561). K–N The MAPKs signaling pathway in primary hepatocytes (L: n = 3, P = 0.006622, 0.031933, 0.00018, 0.305339, 0.000038, 0.520874, 0.0001, 0.917025; N: n = 3, P = 0.000368, 0.046641, 0.000543, 0.810961, 0.002784, 0.717269, 0.000125, 0.619467). O–R The apoptosis signaling pathway in primary hepatocytes (P: n = 3, P = 0.000822, 0.005915, 0.010552, 0.032551, 0.000129, 0.00401; R: n = 3, P = 0.00005, 0.015607, 0.004799, 0.002158, 0.000039, 0.045242). Data are showed as mean ± SD. Three biologically independent experiments. Source data are provided as a Source data file. AdFlag Gene overexpression negative control adenovirus, AdNNMT NNMT overexpression adenovirus, AdScramble Gene knockdown negative control adenovirus, AdshNNMT NNMT knockdown adenovirus, BAX BCL2 associated X protein, BCL2 B cell lymphoma 2, C-Casp3 Cleaved caspase-3, H/R Hypoxia and reoxygenation, *Il1β* Interleukin 1beta, *Il6* Interleukin 6, LDH Lactate dehydrogenase, *Mip2* Macrophage Inflammatory Protein 2, NOR Normoxia, *Tnfα* Tumor necrosis factor α.

**Fig. 3. Hepatocyte-specific *Nnmt* overexpression protected against liver injury, inflammation and apoptosis induced by ischemia-reperfusion.**
A Immunohistochemical staining of NNMT in the livers (scale bar: 100 μm) (n = 10, P = 0.009861). B Illustration of the experimental procedures. C The serum transaminase levels in mice (n = 5, P = 0.000001, 0.004772, 0.0000002, 0.001296). D The serum levels of inflammation cytokines in mice (n = 5, P = 0.0000001, 0.000317, 0.000013, 0.012379, 0.000018, 0.006009, 0.00000001, 0.000015). E The mRNA level of inflammation cytokines in the liver (n = 5, P = 0.001521, 0.044657, 0.000022, 0.00223, 0.000202, 0.020573, 0.000412, 0.0236). F, G The extent of liver injury and necrosis following HIRI (scale bar: 100 μm) (n = 5, P = 0.001036, 0.039969). H, I The population of Ly6G- and CD11b-positive cells in the liver (scale bar: 50 μm) (n = 5, P = 0.0000005, 0.001377, 0.00000002, 0.000236). J, K The NF-κB signaling pathway in the liver (n = 5, P = 0.00000004, 0.002119, 0.000147, 0.018743, 0.000274, 0.000422, 0.000002, 0.000755). L, M The JNK signaling pathway in the liver (n = 5, P = 0.000149, 0.012319). N, O The apoptosis signaling pathway in the liver (n = 5, P = 0.000005, 0.002495, 0.000592, 0.01251, 0.0000000096, 0.000143). P, Q The population of TUNEL-positive cells in the liver (scale bar: 50 μm) (n = 5, P = 0.0000000004). Data are presented as mean ± SD. Three biologically independent experiments. Source data are provided as a Source data file. Figure 3B was created in BioRender. Bing, Y. (2025) https://BioRender.com/vesbjfg. ALT Alann amino transferase, AST Aspartate amino transferase, BAX BCL2 associated X protein, BCL2 B cell lymphoma 2, C-Casp3 Cleaved caspase-3, CD11b Integrin subunit alpha M, H&E Hematoxylin & eosin, IHC Immunohistochemistry, *Il1β*/IL-1β Interleukin 1beta, *Il6*/IL-6 Interleukin 6, IR Ischemia reperfusion, LDH Lactate dehydrogenase, Ly6G Lymphocyte antigen 6 complex locus G, *Mip2*/MIP-2 Macrophage Inflammatory Protein 2, NNMT-HTG NNMT hepatocyte transgene mouse, NTG Non-transgenic mouse, *Tnfα*/TNF-α tumor necrosis factor α, TUNEL Terminal dUTP Nick-End Labeling.

**Fig. 4. Hepatocyte-specific *Nnmt* knockout exacerbated liver injury, inflammation and apoptosis induced by ischemia-reperfusion.**
A Immunohistochemical staining of NNMT in the livers (scale bar: 100 μm) (n = 10, P = 0.0000000002). B Illustration of the experimental procedures. C The serum transaminase levels in mice (n = 5, P = 0.0000004, 0.00031, 0.000004, 0.003313). D The serum levels of inflammation cytokines in mice (n = 5, P = 0.00296, 0.0282, 0.000501, 0.032454, 0.001316, 0.00705, 0.00401, 0.04666). E The mRNA level of inflammation cytokines in the liver (n = 5, P = 0.001061, 0.06148, 0.000207 000193, 0.000544, 0.001082, 0.00187, 0.000905). F, G The extent of liver injury and necrosis following HIRI (scale bar: 100 μm) (n = 5, P = 0.000001, 0.002501). H, I The population of Ly6G- and CD11b-positive cells in the liver (scale bar: 50 μm) (n = 5, P = 0.000000001, 0.000471, 0.0000005, 0.006216). J, K The NF-κB signaling pathway in the liver (n = 5, P = 0.00011, 0.016125, 0.00000001, 0.00256, 0.025562, 0.000833, 0.000035, 0.008382). L, M The JNK signaling pathway in the liver (n = 5, P = 0.000082, 0.018456). N, O The apoptosis signaling pathway in the liver (n = 5, P = 0.0000001, 0.038022, 0.008149, 0.012967, 0.000133, 0.037869). P, Q The population of TUNEL-positive cells in the liver (scale bar: 50 μm) (n = 5, P = 0.00000000005, 0.001386). Data are presented as mean ± SD. Three biologically independent experiments. Source data are provided as a Source Data file. Figure 4B was created in BioRender. Bing, Y. (2025) https://BioRender.com/vesbjfg. ALT Alann amino transferase, AST Aspartate amino transferase, BAX BCL2 associated X protein, BCL2 B cell lymphoma 2, C-Casp3 Cleaved caspase-3, CD11b Integrin subunit alpha M, flox/flox the control group of NNMT^ΔHep mouse, H&E Hematoxylin & eosin, IHC Immunohistochemistry, *Il1β*/IL-1β Interleukin 1beta, IR: Ischemia reperfusion, *Il6*/IL-6 Interleukin 6, LDH Lactate dehydrogenase, Ly6G Lymphocyte antigen 6 complex locus G, *Mip2*/MIP-2 Macrophage Inflammatory Protein 2, NNMT Nicotinamide N-methyltransferase, NNMT^ΔHep hepatocyte-specific *Nnmt* knockout mouse, *Tnfα*/TNF-α Tumor necrosis factor α, TUNEL Terminal dUTP Nick-End Labeling.

**Fig. 5. NNMT/1-MNA regulated the AKT/FOXO1/ANGPT2 axis.**
A RNA sequence of NNMT overexpressing hepatocytes under H/R stimulation, as well as in livers from C57BL/6J mice after 1-MNA pretreatment and subsequent HIRI. B Heatmap of cell transcriptome sequencing (n = 3). C Heatmap of tissue transcriptome sequencing (n = 5). D Cell transcriptome sequencing volcano map. E Tissue transcriptome sequencing volcano map. F Venn diagram of differentially expressed genes from both transcriptome sequencing. G Validation of the sequencing results by qRT‒PCR in primary hepatocytes (n = 3, P = 0.000255, 0.466016, 0.000095, 0.000178). H, I The expression of NNMT and ANGPT2 in primary hepatocytes (H: n = 3, P = 0.001665; I: n = 3, P = 0.008948). J KEGG enrichment analysis of primary hepatocyte RNA sequencing. K, L The AKT/FOXO1 signaling pathway in primary hepatocytes (K: n = 3, P = 0.007049, 0.000026, 0.000449; L: n = 3, P = 0.007049, 0.000026, 0.000449). M Validation of the transfection efficiency of the FOXO1 overexpression plasmid (n = 3, P = 0.002413). N FOXO1 mediated the inhibition of ANGPT2 by NNMT/1-MNA during H/R in primary hepatocytes. O–R PI3K/AKT mediated the inhibition of ANGPT2 and FOXO1 by NNMT/1-MNA during H/R in primary hepatocytes (P: n = 3, P = 0.002255, 0.003152, 0.001284, 0.001528, 0.000862, 0.003306; R: n = 3, P = 0.027408, 0.032687, 0.00016, 0.000161, 0.008183, 0.003259). Data are presented as mean ± SD. Three biologically independent experiments. Source data are provided as a Source Data file. Figure 5A was created in BioRender. Bing, Y. (2025) https://BioRender.com/vesbjfg. AdFlag Gene overexpression negative control adenovirus, AdNNMT NNMT overexpression adenovirus, AKT Protein Kinase B, *Angpt2*/ANGPT2 Angiopoietin 2, *Arntl2* Basic helix-loop-helix ARNT like 2, *Creb5* cAMP responsive element binding protein 5, FOXO1 Forhead box O1, H/R Hypoxia and reoxygenation, IR Ischemia reperfusion, 1-MNA N¹-methylnicotinamide, *Nnmt*/NNMT Nicotinamide N-methyltransferase, PI3K/AKT-IN-1 A specific inhibitor of PI3K/AKT signaling pathway.

**Fig. 6. ANGPT2 exacerbated HIRI-induced inflammation, apoptosis and vascular injury.**
A Illustration of the experimental procedures. B, C The levels of serum transaminase and inflammatory cytokines in these mice (B: n = 5, P = 0.005305, 0.001537, 0.142751, 0.006597; C: n = 5, P = 0.028614, 0.001121, 0.011263, 0.014709, 0.003263, 0.004605, 0.004984, 0.002186). D The mRNA level of inflammation cytokines in the liver (n = 5, P = 0.000184, 0.000087, 0.003713, 0.001586, 0.010984, 0.013157, 0.00887, 0.012965). E, F The extent of liver injury and necrosis (scale bar: 100 μm) (n = 5, P = 0.01385, 0.002319). G–I The population of Ly6G- and CD11b-positive cells in the liver (scale bar: 50 μm) (H: n = 5, P = 0.001685, 0.001053; I: n = 5, P = 0.021513, 0.000567). J, K The population of TUNEL-positive cells in the liver (scale bar: 50 μm) (n = 5, P = 0.027668, 0.00986). L, M Immunohistochemical staining of adhesion molecules in the livers (scale bar: 100 μm) (n = 5, P = 0.00511, 0.010282). N The vascular permeability in the liver (n = 5, P = 0.000023, 0.000907). O The secreted ANGPT2 in the culture media of primary hepatocytes (n = 3, P = 0.001076, 0.005631). P The C166 cells were treated with conditioned media obtained from hepatocytes pretreated with NNMT or 1-MNA during H/R. Q, R The NF-κB signaling pathway, JNK signaling pathway and apoptosis signaling pathway in the C166 cells treated with conditional media (n = 3, P = 0.035456, 0.005848, 0.00415, 0.021562, 0.00088, 0.012006, 0.00523, 0.002745, 0.00509, 0.001655, 0.017543, 0.006799, 0.007158, 0.011605). Data are showed as mean ± SD. Three biologically independent experiments. Source data are provided as a Source Data file. Figure 6A,P were created in BioRender. Bing, Y. (2025) https://BioRender.com/vesbjfg. AdANG2 ANGPT2 overexpression adenovirus, AdFlag Gene overexpression negative control adenovirus, AdScramble Gene knockdown negative control adenovirus, AdshANG2 ANGPT2 knockdown adenovirus, ALT Alann amino transferase, ANGPT2 Angiopoietin 2, AST Aspartate amino transferase, BAX BCL2 associated X protein, BCL2 B cell lymphoma 2, C-Casp3 Cleaved caspase-3, CD11b Integrin subunit alpha M, H&E Hematoxylin & eosin, H/R Hypoxia and reoxygenation, IHC Immunohistochemistry, IR Ischemia reperfusion, *Il1β*/IL-1β Interleukin 1 beta, *Il6*/IL-6 Interleukin 6, LDH Lactate dehydrogenase, Ly6G Lymphocyte antigen 6 complex locus G, *Mip2*/MIP-2 Macrophage Inflammatory Protein 2, 1-MNA N¹-methylnicotinamide, NNMT Nicotinamide N-methyltransferase, *Tnfα*/TNF-α Tumor necrosis factor α, TUNEL Terminal dUTP Nick-End Labeling.

**Fig. 7. Knockdown of ANGPT2 alleviated the negative impacts induced by *Nnmt* depletion.**
A Illustration of the experimental procedures. B, C The levels of serum transaminase and inflammatory cytokines in these mice (B: n = 5, P = 0.000329, 0.000408, 0.000335, 0.000904; C: n = 5, P = 0.000804, 0.004003, 0.0000004, 0.000295, 0.001209, 0.00296, 0.000106, 0.000274). D The mRNA level of inflammation cytokines in the liver (n = 5, P = 0.000007, 0.000365, 0.000003, 0.000109, 0.000018, 0.000392, 0.00094, 0.001724). E, F The extent of liver injury and necrosis (scale bar: 100 μm) (n = 5, P = 0.024019, 0.00767). G, I The population of Ly6G- and CD11b-positive cells in the liver (scale bar: 50 μm) (H: n = 5, P = 0.000249, 0.00767; I: n = 5, P = 0.000104, 0.00767). J, K The population of TUNEL-positive cells in the liver (scale bar: 50 μm) (n = 5, P = 0.000168, 0.00767). L, M The NF-κB signaling pathway, JNK signaling pathway and apoptosis signaling pathway in the liver (n = 5, P = 0.000001, 0.000001, 0.000000008, 0.00000005, 0.000008, 0.000013, 0.0000005, 0.000001, 0.0000001, 0.00000007). N, O Immunohistochemical staining of adhesion molecules in the livers (scale bar: 100 μm) (n = 5, P = 0.001681, 0.004893, 0.001125, 0.010131). P The vascular permeability in the liver (n = 5, P = 0.000653, 0.00767). Data are showed as mean ± SD. Three biologically independent experiments. Source data are provided as a Source data file. Figure 7A was created in BioRender. Bing, Y. (2025) https://BioRender.com/vesbjfg. AdScramble Gene knockdown negative control adenovirus, AdshANG2 ANGPT2 knockdown adenovirus, ALT Alann amino transferase, ANGPT2 Angiopoietin 2, AST Aspartate amino transferase, BAX BCL2 associated X protein, BCL2 B cell lymphoma 2, C-Casp3 Cleaved caspase-3, CD11b Integrin subunit alpha M, flox/flox The control group of NNMT^ΔHep mouse, H&E Hematoxylin & eosin, IHC Immunohistochemistry, IR Ischemia reperfusion, *Il1β*/IL-1β Interleukin 1 beta, *Il6*/IL-6 Interleukin 6, LDH Lactate dehydrogenase, Ly6G Lymphocyte antigen 6 complex locus G, *Mip2*/MIP-2 Macrophage Inflammatory Protein 2, NNMT^ΔHep hepatocyte-specific *Nnmt* knockout mouse, NNMT Nicotinamide N-methyltransferase, *Tnfα*/TNF-α Tumor necrosis factor α, TUNEL Terminal dUTP Nick-End Labeling).

**Fig. 8. The general schematic diagram created with BioRender.**
Figure 8 was created using BioRender.com (https://BioRender.com/vesbjfg) and is released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license (https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en).

See this image and copyright information in PMC

References

1. Yang, W., Chen, J., Meng, Y., Chen, Z. & Yang, J. Novel targets for treating ischemia-reperfusion injury in the liver. Int. J. Mol. Sci. 19, 1302 (2018). - PMC - PubMed
1. Zhai, Y., Petrowsky, H., Hong, J. C., Busuttil, R. W. & Kupiec-Weglinski, J. W. Ischaemia-reperfusion injury in liver transplantation-from bench to bedside. Nat. Rev. Gastroenterol. Hepatol.10, 79–89 (2013). - PMC - PubMed
1. Gao, F. et al. Targeting the hepatic microenvironment to improve ischemia/reperfusion injury: new insights into the immune and metabolic compartments. Aging Dis.13, 1196–1214 (2022). - PMC - PubMed
1. Tang, S. P. et al. Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death. Front. Immunol.13, 870239 (2022). - PMC - PubMed
1. Llacuna, L. et al. Reactive oxygen species mediate liver injury through parenchymal nuclear factor-kappaB inactivation in prolonged ischemia/reperfusion. Am. J. Pathol.174, 1776–1785 (2009). - PMC - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

82370643/National Natural Science Foundation of China (National Science Foundation of China)

LinkOut - more resources

Full Text Sources
- PubMed Central
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous