Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Alleviates Sepsis-Induced Cardiomyopathy by Inhibiting Pyroptosis
-
Guorong Liu
,
Saifeng Chen
,
Xiaoyan Yuan
,
Guo Chen
,
Lei Xu
,
Xinmeichen Meng
,
Kun Wu
,
Dongfeng Guo
Abstract
Background: Sepsis-induced cardiomyopathy (SIC) is a common complication of sepsis accompanied by high prevalence and mortality in sepsis patients. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor, and it exerts critical functions in various diseases, including heart diseases, while its effect on SIC remains elusive. Hence, we aimed to investigate the action of MANF on SIC.
Methods: This study was under the guidance of Gongli Hospital, Shanghai, China from January 2021 to December 2021. H9c2 cells and mice were induced by LPS to establish SIC in vitro and in vivo models. qRT-PCR and Western blot were used to determine gene and protein expressions. The levels of MANF, Interleukin-1β (IL-1β), Interleukin 18 (IL-18), creatine kinase-MB (CK-MB), and cardiac troponin I (cTn I) were detected using ELISA assay. Cell pyroptosis determination was performed by flow cytometry. The DCFDA assay kit was used to determine ROS production.
Results: In SIC in vitro model, LPS induced cell pyroptosis (P<0.001) and ROS accumulation (P<0.001). Besides, MANF was decreased in LPS-induced H9c2 cells (P<0.001) and SIC patients (P<0.001). In addition, overexpression of MANF ameliorated SIC-induced injury in H9C2 cells (P<0.001). Furthermore, inhibition of NLRP3 rescued the function of MANF on SIC-induced injury in H9C2 cells (P<0.001). Moreover, enforced MANF suppressed the SIC-induced injury in vivo model (P<0.001).
Conclusion: MANF was down-regulated in SIC. Overexpressed MANF ameliorated the SIC injury by inhibiting NLRP3-mediated pyroptosis.
1. Hollenberg SM and Singer M (2021). Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol, 18: 424-434. doi: 10.1038/s41569-020-00492-2
2. Li N, Zhou H, Wu H, et al (2019). STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol, 24: 101215. doi: 10.1016/j.redox.2019.101215
3. Huang SH, Xu M, Wu HM, et al (2018). Isoquercitrin Attenuated Cardiac Dysfunction Via AMPKα-Dependent Pathways in LPS-Treated Mice. Mol Nutr Food Res, 62: e1800955. doi: 10.1002/mnfr.201800955
4. Wei WY, Ma ZG, Zhang N, et al (2018). Overexpression of CTRP3 protects against sepsis-induced myocardial dysfunction in mice. Mol Cell Endocrinol, 476: 27-36. doi: 10.1016/j.mce.2018.04.006
5. Beesley SJ, Weber G, Sarge T, et al (2018). Septic Cardiomyopathy. Crit Care Med, 46: 625-634. doi: 10.1097/ccm.0000000000002851
6. L'Heureux M, Sternberg M, Brath L, et al (2020). Sepsis-Induced Cardiomyopathy: a Comprehensive Review. Curr Cardiol Rep, 22: 35. doi: 10.1007/s11886-020-01277-2
7. Antonucci E, Fiaccadori E, Donadello K, et al (2014). Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care, 29: 500-11. doi: 10.1016/j.jcrc.2014.03.028
8. Lv X and Wang H (2016). Pathophysiology of sepsis-induced myocardial dysfunction. Mil Med Res, 3: 30. doi: 10.1186/s40779-016-0099-9
9. Han X, Chen D, Liufu N, et al (2020). MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated Receptor-α. Oxid Med Cell Longev, 2020: 7413693. doi: 10.1155/2020/7413693
10. Li Q, Zhang M, Zhao Y, et al (2021). Irisin Protects Against LPS-Stressed Cardiac Damage Through Inhibiting Inflammation, Apoptosis, and Pyroptosis. Shock, 56: 1009-1018. doi: 10.1097/shk.0000000000001775
11. Yang S, Li S and Li XJ (2018). MANF: A New Player in the Control of Energy Homeostasis, and Beyond. Front Physiol, 9: 1725. doi: 10.3389/fphys.2018.01725
12. Wang Y, Wen W, Li H, et al (2021). MANF is neuroprotective against ethanol-induced neurodegeneration through ameliorating ER stress. Neurobiol Dis, 148: 105216. doi: 10.1016/j.nbd.2020.105216
13. Liu J, Wu Z, Han D, et al (2020). Mesencephalic Astrocyte-Derived Neurotrophic Factor Inhibits Liver Cancer Through Small Ubiquitin-Related Modifier (SUMO)ylation-Related Suppression of NF-κB/Snail Signaling Pathway and Epithelial-Mesenchymal Transition. Hepatology, 71: 1262-1278. doi: 10.1002/hep.30917
14. Hou C, Wang D, Li X, et al (2019). MANF regulates splenic macrophage differentiation in mice. Immunol Lett, 212: 37-45. doi: 10.1016/j.imlet.2019.06.007
15. Wang C, Bao Q, Hou C, et al (2021). Mono-macrophage-Derived MANF Alleviates Bacterial Myocarditis by Inhibiting NF-kappaB Activation and Myocardial Inflammation. Inflammation, 44: 1916-1926. doi: 10.1007/s10753-021-01469-0
16. Arrieta A, Blackwood EA, Stauffer WT, et al (2020). Mesencephalic astrocyte-derived neurotrophic factor is an ER-resident chaperone that protects against reductive stress in the heart. J Biol Chem, 295: 7566-7583. doi: 10.1074/jbc.RA120.013345
17. Zhu W, Li J, Liu Y, et al (2016). Mesencephalic astrocyte-derived neurotrophic factor attenuates inflammatory responses in lipopolysaccharide-induced neural stem cells by regulating NF-κB and phosphorylation of p38-MAPKs pathways. Immunopharmacol Immunotoxicol, 38: 205-13. doi: 10.3109/08923973.2016.1168433
18. Ernst O, Khan MM, Oyler BL, et al (2021). Species-Specific Endotoxin Stimulus Determines Toll-Like Receptor 4- and Caspase 11-Mediated Pathway Activation Characteristics. mSystems, 6: e0030621. doi: 10.1128/mSystems.00306-21
19. Luo Q, Liu R, Qu K, et al (2021). Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17. Eur J Med Res, 26: 70. doi: 10.1186/s40001-021-00536-4
20. Gross O, Poeck H, Bscheider M, et al (2009). Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature, 459: 433-6. doi: 10.1038/nature07965
21. Jia C, Zhang J, Chen H, et al (2019). Endothelial cell pyroptosis plays an important role in Kawasaki disease via HMGB1/RAGE/cathespin B signaling pathway and NLRP3 inflammasome activation. Cell Death Dis, 10: 778. doi: 10.1038/s41419-019-2021-3
22. Wu X, Zhang H, Qi W, et al (2018). Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis. Cell Death Dis, 9: 171. doi: 10.1038/s41419-017-0257-3
23. Yang M, Lv H, Liu Q, et al (2020). Colchicine Alleviates Cholesterol Crystal-Induced Endothelial Cell Pyroptosis through Activating AMPK/SIRT1 Pathway. Oxid Med Cell Longev, 2020: 9173530. doi: 10.1155/2020/9173530
24. An L, Yang T, Zhong Y, et al (2021). Molecular pathways in sepsis-induced cardiomyocyte pyroptosis: Novel finding on long non-coding RNA ZFAS1/miR-138-5p/SESN2 axis. Immunol Lett, 238: 47-56. doi: 10.1016/j.imlet.2021.07.003
25. Bao J, Ye C, Zheng Z, et al (2018). Fmr1 protects cardiomyocytes against lipopolysaccharide-induced myocardial injury. Exp Ther Med, 16: 1825-1833. doi: 10.3892/etm.2018.6386
26. Bertheloot D, Latz E and Franklin BS (2021). Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol, 18: 1106-1121. doi: 10.1038/s41423-020-00630-3
27. Kovaleva V, Yu LY, Ivanova L, et al (2023). MANF regulates neuronal survival and UPR through its ER-located receptor IRE1α. Cell Rep, 42: 112066. doi: 10.1016/j.celrep.2023.112066
28. Lerner AG, Upton JP, Praveen PV, et al (2012). IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab, 16: 250-64. doi: 10.1016/j.cmet.2012.07.007
29. Nageh T, Sherwood RA, Harris BM, et al (2003). Cardiac troponin T and I and creatine kinase-MB as markers of myocardial injury and predictors of outcome following percutaneous coronary intervention. Int J Cardiol, 92: 285-93. doi: 10.1016/s0167-5273(03)00105-0
30. Shi H, Gao Y, Dong Z, et al (2021). GSDMD-Mediated Cardiomyocyte Pyroptosis Promotes Myocardial I/R Injury. Circ Res, 129: 383-396. doi: 10.1161/circresaha.120.318629
31. Zeng C, Wang R and Tan H (2019). Role of Pyroptosis in Cardiovascular Diseases and its Therapeutic Implications. Int J Biol Sci, 15: 1345-1357. doi: 10.7150/ijbs.33568
2. Li N, Zhou H, Wu H, et al (2019). STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol, 24: 101215. doi: 10.1016/j.redox.2019.101215
3. Huang SH, Xu M, Wu HM, et al (2018). Isoquercitrin Attenuated Cardiac Dysfunction Via AMPKα-Dependent Pathways in LPS-Treated Mice. Mol Nutr Food Res, 62: e1800955. doi: 10.1002/mnfr.201800955
4. Wei WY, Ma ZG, Zhang N, et al (2018). Overexpression of CTRP3 protects against sepsis-induced myocardial dysfunction in mice. Mol Cell Endocrinol, 476: 27-36. doi: 10.1016/j.mce.2018.04.006
5. Beesley SJ, Weber G, Sarge T, et al (2018). Septic Cardiomyopathy. Crit Care Med, 46: 625-634. doi: 10.1097/ccm.0000000000002851
6. L'Heureux M, Sternberg M, Brath L, et al (2020). Sepsis-Induced Cardiomyopathy: a Comprehensive Review. Curr Cardiol Rep, 22: 35. doi: 10.1007/s11886-020-01277-2
7. Antonucci E, Fiaccadori E, Donadello K, et al (2014). Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care, 29: 500-11. doi: 10.1016/j.jcrc.2014.03.028
8. Lv X and Wang H (2016). Pathophysiology of sepsis-induced myocardial dysfunction. Mil Med Res, 3: 30. doi: 10.1186/s40779-016-0099-9
9. Han X, Chen D, Liufu N, et al (2020). MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated Receptor-α. Oxid Med Cell Longev, 2020: 7413693. doi: 10.1155/2020/7413693
10. Li Q, Zhang M, Zhao Y, et al (2021). Irisin Protects Against LPS-Stressed Cardiac Damage Through Inhibiting Inflammation, Apoptosis, and Pyroptosis. Shock, 56: 1009-1018. doi: 10.1097/shk.0000000000001775
11. Yang S, Li S and Li XJ (2018). MANF: A New Player in the Control of Energy Homeostasis, and Beyond. Front Physiol, 9: 1725. doi: 10.3389/fphys.2018.01725
12. Wang Y, Wen W, Li H, et al (2021). MANF is neuroprotective against ethanol-induced neurodegeneration through ameliorating ER stress. Neurobiol Dis, 148: 105216. doi: 10.1016/j.nbd.2020.105216
13. Liu J, Wu Z, Han D, et al (2020). Mesencephalic Astrocyte-Derived Neurotrophic Factor Inhibits Liver Cancer Through Small Ubiquitin-Related Modifier (SUMO)ylation-Related Suppression of NF-κB/Snail Signaling Pathway and Epithelial-Mesenchymal Transition. Hepatology, 71: 1262-1278. doi: 10.1002/hep.30917
14. Hou C, Wang D, Li X, et al (2019). MANF regulates splenic macrophage differentiation in mice. Immunol Lett, 212: 37-45. doi: 10.1016/j.imlet.2019.06.007
15. Wang C, Bao Q, Hou C, et al (2021). Mono-macrophage-Derived MANF Alleviates Bacterial Myocarditis by Inhibiting NF-kappaB Activation and Myocardial Inflammation. Inflammation, 44: 1916-1926. doi: 10.1007/s10753-021-01469-0
16. Arrieta A, Blackwood EA, Stauffer WT, et al (2020). Mesencephalic astrocyte-derived neurotrophic factor is an ER-resident chaperone that protects against reductive stress in the heart. J Biol Chem, 295: 7566-7583. doi: 10.1074/jbc.RA120.013345
17. Zhu W, Li J, Liu Y, et al (2016). Mesencephalic astrocyte-derived neurotrophic factor attenuates inflammatory responses in lipopolysaccharide-induced neural stem cells by regulating NF-κB and phosphorylation of p38-MAPKs pathways. Immunopharmacol Immunotoxicol, 38: 205-13. doi: 10.3109/08923973.2016.1168433
18. Ernst O, Khan MM, Oyler BL, et al (2021). Species-Specific Endotoxin Stimulus Determines Toll-Like Receptor 4- and Caspase 11-Mediated Pathway Activation Characteristics. mSystems, 6: e0030621. doi: 10.1128/mSystems.00306-21
19. Luo Q, Liu R, Qu K, et al (2021). Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17. Eur J Med Res, 26: 70. doi: 10.1186/s40001-021-00536-4
20. Gross O, Poeck H, Bscheider M, et al (2009). Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature, 459: 433-6. doi: 10.1038/nature07965
21. Jia C, Zhang J, Chen H, et al (2019). Endothelial cell pyroptosis plays an important role in Kawasaki disease via HMGB1/RAGE/cathespin B signaling pathway and NLRP3 inflammasome activation. Cell Death Dis, 10: 778. doi: 10.1038/s41419-019-2021-3
22. Wu X, Zhang H, Qi W, et al (2018). Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis. Cell Death Dis, 9: 171. doi: 10.1038/s41419-017-0257-3
23. Yang M, Lv H, Liu Q, et al (2020). Colchicine Alleviates Cholesterol Crystal-Induced Endothelial Cell Pyroptosis through Activating AMPK/SIRT1 Pathway. Oxid Med Cell Longev, 2020: 9173530. doi: 10.1155/2020/9173530
24. An L, Yang T, Zhong Y, et al (2021). Molecular pathways in sepsis-induced cardiomyocyte pyroptosis: Novel finding on long non-coding RNA ZFAS1/miR-138-5p/SESN2 axis. Immunol Lett, 238: 47-56. doi: 10.1016/j.imlet.2021.07.003
25. Bao J, Ye C, Zheng Z, et al (2018). Fmr1 protects cardiomyocytes against lipopolysaccharide-induced myocardial injury. Exp Ther Med, 16: 1825-1833. doi: 10.3892/etm.2018.6386
26. Bertheloot D, Latz E and Franklin BS (2021). Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol, 18: 1106-1121. doi: 10.1038/s41423-020-00630-3
27. Kovaleva V, Yu LY, Ivanova L, et al (2023). MANF regulates neuronal survival and UPR through its ER-located receptor IRE1α. Cell Rep, 42: 112066. doi: 10.1016/j.celrep.2023.112066
28. Lerner AG, Upton JP, Praveen PV, et al (2012). IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab, 16: 250-64. doi: 10.1016/j.cmet.2012.07.007
29. Nageh T, Sherwood RA, Harris BM, et al (2003). Cardiac troponin T and I and creatine kinase-MB as markers of myocardial injury and predictors of outcome following percutaneous coronary intervention. Int J Cardiol, 92: 285-93. doi: 10.1016/s0167-5273(03)00105-0
30. Shi H, Gao Y, Dong Z, et al (2021). GSDMD-Mediated Cardiomyocyte Pyroptosis Promotes Myocardial I/R Injury. Circ Res, 129: 383-396. doi: 10.1161/circresaha.120.318629
31. Zeng C, Wang R and Tan H (2019). Role of Pyroptosis in Cardiovascular Diseases and its Therapeutic Implications. Int J Biol Sci, 15: 1345-1357. doi: 10.7150/ijbs.33568
| Files | ||
| Issue | Vol 52 No 11 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i11.14052 | |
| Keywords | ||
| Sepsis-induced cardiomyopathy Pyroptosis | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Liu G, Chen S, Yuan X, Chen G, Xu L, Meng X, Wu K, Guo D. Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Alleviates Sepsis-Induced Cardiomyopathy by Inhibiting Pyroptosis. Iran J Public Health. 2023;52(11):2380-2389.
