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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

MiR-148b Caused Liver Injury in Rats with Traumatic Hemorrhagic Shock by Inhibiting SIRT6 Expression

Author(s): Xiongfei Ma and Mingchen Liu*

Volume 24, Issue 11, 2024

Published on: 19 October, 2023

Page: [1390 - 1400] Pages: 11

DOI: 10.2174/1566524023666230816112629

Price: $65

Open Access Journals Promotions 2
Abstract

Background: The purpose of this study was to investigate the role of miR- 148b in liver injury in rats with traumatic hemorrhagic shock (THS) and to elucidate its potential mechanism.

Methods: The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of rats were detected by enzyme-linked immune sorbent assay (ELISA), and the injury of rat liver was analyzed by hematoxylin-eosin (H&E) staining. Apoptosis of rat hepatocytes and normal rat liver cell line (BRL3A) was identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and flow cytometry, respectively. MiR-148b and sirtuin 6 (SIRT6) expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Lactate dehydrogenase (LDH) content and cell viability were measured by commercial kits and cell counting kit-8 (CCK-8) assay, respectively. The binding sites of miR-148b and SIRT6 were predicted by the Starbase database and verified by dual luciferase reporter assay.

Results: MiR-148b expression in THS rats or ischemia-reperfusion (I/R)-treated cells was higher than in the control group. Overexpression of miR-148b further promoted the effects of I/R, which enhanced the levels of ALT, AST and LDH, cell apoptosis of liver tissue or BRL3A cells and decreased the expression of SITR6. Besides, miR-148b negatively correlated with SIRT6, and upregulated the expression of SIRT6 could partly reverse the effect of miR-148b.

Conclusion: Hepatocyte injury induced by I/R was achieved by regulating miR-148b /SIRT6 axis.

Keywords: miR-148b, SIRT6, traumatic hemorrhagic shock, I/R, apoptosis, liver injury, alanine aminotransferase.

[1]
Bellamy RF. The causes of death in conventional land warfare: Implications for combat casualty care research. Mil Med 1984; 149(2): 55-62.
[PMID: 6427656]
[2]
Liu L, Tian K. Small doses of arginine vasopressin in combination with norepinephrine "buy" time for definitive treatment for uncontrolled hemorrhagic shock in rats. Shock 2013; 40(5): 398-406.
[PMID: 24089002]
[3]
Lei Y, Peng X, Liu L, Dong Z, Li T. Beneficial effect of cyclosporine A on traumatic hemorrhagic shock. J Surg Res 2015; 195(2): 529-40.
[PMID: 25752214]
[4]
Yang G, Peng X. 4-phenylbutyrate benefits traumatic hemorrhagic shock in rats by attenuating oxidative stress, not by attenuating endoplasmic reticulum stress. Crit Care Med 2016; 44(7): e477-91.
[PMID: 26646458]
[5]
Taniguchi TA-O, Fujimoto Y, Yawata H, Horiguchi M, An B, Takegami T, et al. Renal venous congestion following hemorrhagic shock due to traumatic liver injury. CEN Case Rep 2021; 10(2): 178-83.
[http://dx.doi.org/10.1007/s13730-020-00540-3] [PMID: 33038002]
[6]
Liu H, Xuefei X, Chuanzheng S, et al. Systemic inflammation and multiple organ injury in traumatic hemorrhagic shock. Front Biosci 2015; 20(6): 927-33.
[http://dx.doi.org/10.2741/4347] [PMID: 25961533]
[7]
Gu M, Wang J, Wang Y, Xu Y, Zhang Y, Wu W, et al. MiR-147b inhibits cell viability and promotes apoptosis of rat H9c2 cardiomyocytes via down-regulating KLF13 expression. Acta Biochim Biophys Sin 2018; 50(3): 288-97.
[http://dx.doi.org/10.1093/abbs/gmx144.] [PMID: 29377979]
[8]
Zhang JA-O, Xu Y, Liu H, Pan Z. MicroRNAs in ovarian follicular atresia and granulosa cell apoptosis. Reprod Biol Endocrinol 2019; 17(1): 9.
[9]
Huang X, Le QT, Giaccia AJ. MiR-210 - micromanager of the hypoxia pathway. Trends Mol Med 2010; 16(5): 230-7.
[http://dx.doi.org/10.1016/j.molmed.2010.03.004] [PMID: 20434954]
[10]
Puisségur M-P, Mazure NM, Bertero T, et al. miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death Differ 2011; 18(3): 465-78.
[http://dx.doi.org/10.1038/cdd.2010.119] [PMID: 20885442]
[11]
Jianmin L, Chanyuan P, Chao T, Wenwen T, Hui L, Jing G. The reaction pathway of miR-30c-5p activates lipopolysaccharide promoting the course of traumatic and hemorrhagic shock acute lung injury. Biomed Res Int 2022; 2022: 3330552.
[12]
Yan L, Xiaoyong P, Yi H, Mingying X, Tao L, Liangming L, et al. The calcilytic drug Calhex-231 ameliorates vascular hyporesponsiveness in traumatic hemorrhagic shock by inhibiting oxidative stress and miR-208a-Mediated mitochondrial fission. Oxid Med Cell Longev 2020; 20202: 4132785.
[http://dx.doi.org/10.1155/2020/4132785] [PMID: 33343806]
[13]
Vyas HS, Upadhyay KK, Devkar RV. miRNAs Signatures in patients with acute liver injury: Clinical concerns and correlations. Curr Mol Med 2020; 20(5): 325-35.
[14]
Klieser E, Mayr C, Kiesslich T, Wissniowski T, Fazio PD, Neureiter D, et al. The crosstalk of miRNA and oxidative stress in the liver: From physiology to pathology and clinical implications. Int J Mol Sci 2019; 20(21): 5266.
[http://dx.doi.org/10.3390/ijms20215266]
[15]
Wang X, He Y, Mackowiak B, Gao B. MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases. Gut 2021; 70(4): 784-95.
[http://dx.doi.org/10.1136/gutjnl-2020-322526] [PMID: 33127832]
[16]
Yang MA-O, Kong DY, Chen JC. Inhibition of miR-148b ameliorates myocardial ischemia/reperfusion injury via regulation of Wnt/β-catenin signaling pathway. J Cell Physiol 2019; 234(10): 17757-66.
[http://dx.doi.org/10.1002/jcp.28401] [PMID: 30820984]
[17]
Pan WM, Wang H, Zhang XF, et al. miR-210 participates in hepatic ischemia reperfusion injury by forming a negative feedback loop with SMAD4. Hepatology 2020; 72(6): 2134-48.
[http://dx.doi.org/10.1002/hep.31221] [PMID: 32155285]
[18]
Zhang S, Jiang S, Wang H, Di W, Deng C, Jin Z, et al. SIRT6 protects against hepatic ischemia/reperfusion injury by inhibiting apoptosis and autophagy related cell death. Free Radic Biol Med 2018; 115: 18-30.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.11.005.] [PMID: 29129519]
[19]
Owattanapanich N, Chittawatanarat K, Benyakorn T, Sirikun J. Risks and benefits of hypotensive resuscitation in patients with traumatic hemorrhagic shock: A meta-analysis. Scand J Trauma Resusc Emerg Med 20108; 26(1): 107.
[http://dx.doi.org/10.1186/s13049-018-0572-4.] [PMID: 30558650]
[20]
Tran A, Yates J. Permissive hypotension versus conventional resuscitation strategies in adult trauma patients with hemorrhagic shock: A systematic review and meta-analysis of randomized controlled trials. J Trauma Acute Care Surg 2018; 84(5): 802-8.
[http://dx.doi.org/10.1097/TA.0000000000001816.] [PMID: 29370058]
[21]
Hutchings SD, Naumann DN, Hopkins P, Mellis C, Riozzi P, Sartini S, et al. Microcirculatory impairment is associated with multiple organ dysfunction following traumatic hemorrhagic shock: The MICROSHOCK study. Crit Care Med 2018; 46(9): e889-96.
[22]
Chico-Fernández M, Barea-Mendoza JA, Pérez-Bárcena J, García-Sáez I, Quintana-Díaz M, Marina L, et al. Concomitant traumatic brain injury and hemorrhagic shock: Outcomes using the spanish trauma icu registry (RETRAUCI). Am Surg 2021; 87(3): 370-5.
[23]
Tachon G, Harrois A. Microcirculatory alterations in traumatic hemorrhagic shock. Crit Care Med 2014; 42(6): 1433-41.
[24]
Khattab H, Fouad A, Hamza M, Mohey MA, El-Akel W, Ghoneim H, et al. Relation of ALT and AST levels to the histopathological changes in liver biopsies of patients with chronic hepatitis C genotype 4. Arab J Gastroenterol 2015; 16(2): 50-3.
[25]
Xiong X, Ren Y, Cui Y, Li R, Wang C, Zhang Y. Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation. Biomed Pharmacother 2017; 96: 1292-8.
[26]
Mylonas AI, Orfanos NF, Karmaniolou II, Lolis ED, Stergiou EP, Papalois AE, et al. The effects of hemorrhagic shock secondary to hepatectomy in a swine model. J Surg Res 2015; 195(1): 228-34.
[27]
Saidi RF, Kenari SK. Liver ischemia/reperfusion injury: An overview. J Invest Surg 2014; 27(6): 366-79.
[28]
Baik SW, Park BS, Kim YH, Kim YD, Kim CH, Yoon JY, et al. Effects of remifentanil preconditioning on osteoblasts under hypoxia-reoxygenation condition. Int J Med Sci 2015; 12(7): 583-9.
[29]
Zhang L, Li C, Cao L, Li H, Zou H, Li H, et al. microRNA-877 inhibits malignant progression of colorectal cancer by directly targeting MTDH and regulating the PTEN/Akt pathway. Cancer Manag Res 2019; 11: 2769-81.
[30]
Zhu J, Zhang C, Qing Y, et al. Genistein induces apoptosis by stabilizing intracellular p53 protein through an APE1-mediated pathway. Free Radic Biol Med 2015; 86: 209-18.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.05.030] [PMID: 26032169]
[31]
Liu Q, Xu Y, Wei S, Gao W, Chen L, Zhou T, et al. miRNA-148b suppresses hepatic cancer stem cell by targeting neuropilin-1. Biosci Rep 2015; 35(4): e00229.
[http://dx.doi.org/10.1042/BSR20150084]
[32]
Zhu Y, Ni T, Lin J, Zhang C, Zheng L, Luo M. Long non-coding RNA H19, a negative regulator of microRNA-148b-3p, participates in hypoxia stress in human hepatic sinusoidal endothelial cells via NOX4 and eNOS/NO signaling. Biochimie 2019; 163: 128-36.
[33]
Yao L, Chen H, Wu Q, Xie K. Hydrogen-rich saline alleviates inflammation and apoptosis in myocardial I/R injury via PINK-mediated autophagy. Int J Mol Med 2019; 44(3): 1048-62.
[34]
An Y, Wang B, Wang X, Dong G, Jia J, Yang Q. SIRT1 inhibits chemoresistance and cancer stemness of gastric cancer by initiating an AMPK/FOXO3 positive feedback loop. Cell Death Dis 2020; 11(2): 115.
[http://dx.doi.org/10.1038/s41419-020-2308-4] [PMID: 32051395]
[35]
Li M, Zhang Z, Liu B, Chen L, Wang M. LncRNA GAS5 upregulates miR-214 through methylation to participate in cell apoptosis of sepsis. Arch Physiol Biochem 2022; 128(5): 1259-64.
[http://dx.doi.org/10.1080/13813455.2020.1764051.] [PMID: 32551941]

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