Integrated Analysis Reveals S100a8/a9 Regulates Autophagy and Apoptosis Through the MAPK and PI3K-AKT Signaling Pathway in the Early Stage of Myocardial Infarction

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Jun 24

PMID 35741040

Authors

Weijue Yi

Rongli Zhu

Xiuyang Hou

Fengmin Wu

Rui Feng

Affiliations

Soon will be listed here.

Abstract

Myocardial infarction (MI), a type of coronary heart disease, has had a significantly increased incidence in recent years. The balance of cardiomyocyte apoptosis and autophagy after MI is one of the main determinants of patient prognosis. Both affect myocardial fibrosis and ventricular remodeling and regulate cell survival. However, there are few studies on the regulation mechanism of cardiomyocyte autophagy and apoptosis in the early stage after MI. In this study, based on analyzing the scRNA-seq and mRNA-seq data of mice in the early stage of MI, we found that the expression of S100a8 and S100a9 increased first and then decreased in the early stage of MI, and their expression level changed with the number of neutrophils. Further, through the functional enrichment analysis of the differentially expressed genes, we found that S100a8 and S100a9 were simultaneously associated with autophagy and apoptosis and could regulate autophagy and apoptosis of cardiomyocytes through MAPK or PI3K-AKT signaling pathways. This study provides valuable insights for clarifying the pathogenesis of early stage MI and improving its early treatment.

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References

Vafadarnejad E, Rizzo G, Krampert L, Arampatzi P, Arias-Loza A, Nazzal Y . Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction. Circ Res. 2020; 127(9):e232-e249. DOI: 10.1161/CIRCRESAHA.120.317200. View

Xiao X, Yang C, Qu S, Shao Y, Zhou C, Chao R . S100 proteins in atherosclerosis. Clin Chim Acta. 2019; 502:293-304. DOI: 10.1016/j.cca.2019.11.019. View

Kong P, Christia P, Frangogiannis N . The pathogenesis of cardiac fibrosis. Cell Mol Life Sci. 2013; 71(4):549-74. PMC: 3769482. DOI: 10.1007/s00018-013-1349-6. View

Yang M, Zeng P, Kang R, Yu Y, Yang L, Tang D . S100A8 contributes to drug resistance by promoting autophagy in leukemia cells. PLoS One. 2014; 9(5):e97242. PMC: 4018274. DOI: 10.1371/journal.pone.0097242. View

Muller I, Vogl T, Kuhl U, Krannich A, Banks A, Trippel T . Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis. ESC Heart Fail. 2020; 7(4):1442-1451. PMC: 7373886. DOI: 10.1002/ehf2.12760. View

Boyd J, Kan B, Roberts H, Wang Y, Walley K . S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products. Circ Res. 2008; 102(10):1239-46. DOI: 10.1161/CIRCRESAHA.107.167544. View

Moradpoor R, Gharebaghian A, Shahi F, Mousavi A, Salari S, Akbari M . Identification and Validation of Stage-Associated PBMC Biomarkers in Breast Cancer Using MS-Based Proteomics. Front Oncol. 2020; 10:1101. PMC: 7393188. DOI: 10.3389/fonc.2020.01101. View

Boteanu R, Suica V, Uyy E, Ivan L, Cerveanu-Hogas A, Mares R . Short-Term Blockade of Pro-Inflammatory Alarmin S100A9 Favorably Modulates Left Ventricle Proteome and Related Signaling Pathways Involved in Post-Myocardial Infarction Recovery. Int J Mol Sci. 2022; 23(9). PMC: 9103348. DOI: 10.3390/ijms23095289. View

Li Y, Chen B, Yang X, Zhang C, Jiao Y, Li P . S100a8/a9 Signaling Causes Mitochondrial Dysfunction and Cardiomyocyte Death in Response to Ischemic/Reperfusion Injury. Circulation. 2019; 140(9):751-764. DOI: 10.1161/CIRCULATIONAHA.118.039262. View

10.

Bresnick A, Weber D, Zimmer D . S100 proteins in cancer. Nat Rev Cancer. 2015; 15(2):96-109. PMC: 4369764. DOI: 10.1038/nrc3893. View

11.

Hwa Kwon C, Moon H, Park H, Choi J, Park D . S100A8 and S100A9 promotes invasion and migration through p38 mitogen-activated protein kinase-dependent NF-κB activation in gastric cancer cells. Mol Cells. 2013; 35(3):226-34. PMC: 3887919. DOI: 10.1007/s10059-013-2269-x. View

12.

Zhang X, Hou G, Liu A, Xu H, Guan Y, Wu Y . Matrine inhibits the development and progression of ovarian cancer by repressing cancer associated phosphorylation signaling pathways. Cell Death Dis. 2019; 10(10):770. PMC: 6787190. DOI: 10.1038/s41419-019-2013-3. View

13.

Delbridge L, Mellor K, Taylor D, Gottlieb R . Myocardial stress and autophagy: mechanisms and potential therapies. Nat Rev Cardiol. 2017; 14(7):412-425. PMC: 6245608. DOI: 10.1038/nrcardio.2017.35. View

14.

Wang X, Guo Z, Ding Z, Mehta J . Inflammation, Autophagy, and Apoptosis After Myocardial Infarction. J Am Heart Assoc. 2018; 7(9). PMC: 6015297. DOI: 10.1161/JAHA.117.008024. View

15.

Zhang Y, Zha Z, Shen W, Li D, Kang N, Chen Z . Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-κB signaling pathway. Chin Med. 2021; 16(1):11. PMC: 7814617. DOI: 10.1186/s13020-020-00410-1. View

16.

Zhou J, Jiang Y, Chen H, Wu Y, Zhang L . Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Prolif. 2019; 53(2):e12739. PMC: 7046305. DOI: 10.1111/cpr.12739. View

17.

Sciarretta S, Yee D, Nagarajan N, Bianchi F, Saito T, Valenti V . Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction. J Am Coll Cardiol. 2018; 71(18):1999-2010. PMC: 6347412. DOI: 10.1016/j.jacc.2018.02.066. View

18.

Bacmeister L, Schwarzl M, Warnke S, Stoffers B, Blankenberg S, Westermann D . Inflammation and fibrosis in murine models of heart failure. Basic Res Cardiol. 2019; 114(3):19. DOI: 10.1007/s00395-019-0722-5. View

19.

Yokota T, McCourt J, Ma F, Ren S, Li S, Kim T . Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury. Cell. 2020; 182(3):545-562.e23. PMC: 7415659. DOI: 10.1016/j.cell.2020.06.030. View

20.

Ghavami S, Eshragi M, Ande S, Chazin W, Klonisch T, Halayko A . S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res. 2009; 20(3):314-31. PMC: 4161879. DOI: 10.1038/cr.2009.129. View