Down-regulation of MiR-133a-3p Protects Lung Tissue Against Sepsis-induced Acute Respiratory Distress Syndrome by Up-regulating SIRT1

Overview

Journal Arch Med Sci

Specialty General Medicine

Date 2024 Feb 28

PMID 38414466

Authors

Qin Hui

Qi Zhang

Xuan Li

Kundi Wang

Jing Zhang

Zhongshu Zhou

Affiliations

Soon will be listed here.

Abstract

Introduction: MicroRNA-133a-3p (miR-133a-3p) is a potential gene regulator having an important role in the process of inflammation and lung injury. The present work studied the role of miR-133a-3p in sepsis-mediated acute respiratory distress syndrome (ARDS) and the mechanism involved.

Material And Methods: C57BL/6 mice were selected for the study. Protein expression of Bcl-2, cleaved caspase-3 and Bax was assessed by western blot analysis. Expression of mRNA was assessed by RT-PCR. Effects of inflammation were studied by myeloperoxidase (MPO) activity. Quantification of albumin was done by measuring the albumin conjugated with Evan's blue. The alveolar macrophages were separated from the lungs of mice by the bronchoalveolar lavage procedure and were submitted to sepsis challenge ; the macrophages were treated with lipopolysaccharide (LPS).

Results: Treatment of LPS resulted in upregulation of miR-133a-3p in alveolar macrophages. Suppression of miR-133a-3p halted the over-expression of inflammatory cytokines in macrophages and caused remission of histopathologic changes. The ARDS lungs showed a decrease in levels of proinflammatory cytokines and an increase in levels of apoptotic protein, establishing the protective role for miR-133a-3p. The results suggested sirtuin 1 (SIRT1) as a potential target of miR-133a-3p in the macrophages, also showing that expression of SIRT1 was inversely associated with expression of miR-133a-3p. The protective effect of miR-133a-3p down-regulation in LPS-mediated alveolar macrophages and sepsis-induced ARDS could be corrected by a SIRT1 inhibitor.

Conclusions: Down-regulation of miR-133a-3p may exert a protective effect on lung tissue against sepsis-mediated ARDS by up-regulating the levels of SIRT1 via suppressing the inflammatory response and inhibiting the cellular apoptosis in lung tissues.

References

Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T . Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002; 12(9):735-9. DOI: 10.1016/s0960-9822(02)00809-6. View

Lavu S, Boss O, Elliott P, Lambert P . Sirtuins--novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov. 2008; 7(10):841-53. DOI: 10.1038/nrd2665. View

Yang S, Wright J, Bauter M, Seweryniak K, Kode A, Rahman I . Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-kappaB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging. Am J Physiol Lung Cell Mol Physiol. 2006; 292(2):L567-76. DOI: 10.1152/ajplung.00308.2006. View

Koutsoulidou A, Mastroyiannopoulos N, Furling D, Uney J, Phylactou L . Expression of miR-1, miR-133a, miR-133b and miR-206 increases during development of human skeletal muscle. BMC Dev Biol. 2011; 11:34. PMC: 3132729. DOI: 10.1186/1471-213X-11-34. View

Zhang J, Lee S, Shannon S, Gao B, Chen W, Chen A . The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice. J Clin Invest. 2009; 119(10):3048-58. PMC: 2752073. DOI: 10.1172/JCI38902. View

Fan H, Zhao Y, Sun M, Zhu J . Urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, N-acetyl-β-D-glucosaminidase levels and mortality risk in septic patients with acute kidney injury. Arch Med Sci. 2018; 14(6):1381-1386. PMC: 6209703. DOI: 10.5114/aoms.2018.79006. View

Lan C, Shi X, Guo N, Pei H, Zhang H . [Value of serum miR-155-5p and miR-133a-3p expression for the diagnosis and prognosis evaluation of sepsis]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016; 28(8):694-8. DOI: 10.3760/cma.j.issn.2095-4352.2016.08.005. View

Avecillas J, Freire A, Arroliga A . Clinical epidemiology of acute lung injury and acute respiratory distress syndrome: incidence, diagnosis, and outcomes. Clin Chest Med. 2006; 27(4):549-57. DOI: 10.1016/j.ccm.2006.06.001. View

Rossaint J, Zarbock A . Pathogenesis of Multiple Organ Failure in Sepsis. Crit Rev Immunol. 2016; 35(4):277-91. DOI: 10.1615/critrevimmunol.2015015461. View

10.

Vidigal J, Ventura A . The biological functions of miRNAs: lessons from in vivo studies. Trends Cell Biol. 2014; 25(3):137-47. PMC: 4344861. DOI: 10.1016/j.tcb.2014.11.004. View

11.

Laskin D, Pendino K . Macrophages and inflammatory mediators in tissue injury. Annu Rev Pharmacol Toxicol. 1995; 35:655-77. DOI: 10.1146/annurev.pa.35.040195.003255. View

12.

Babiarz J, Ravon M, Sridhar S, Ravindran P, Swanson B, Bitter H . Determination of the human cardiomyocyte mRNA and miRNA differentiation network by fine-scale profiling. Stem Cells Dev. 2011; 21(11):1956-65. PMC: 4048009. DOI: 10.1089/scd.2011.0357. View

13.

Vanden Berghe T, Demon D, Bogaert P, Vandendriessche B, Goethals A, Depuydt B . Simultaneous targeting of IL-1 and IL-18 is required for protection against inflammatory and septic shock. Am J Respir Crit Care Med. 2014; 189(3):282-91. DOI: 10.1164/rccm.201308-1535OC. View

14.

Duran-Bedolla J, Montes de Oca-Sandoval M, Saldana-Navor V, Villalobos-Silva J, Rodriguez M, Rivas-Arancibia S . Sepsis, mitochondrial failure and multiple organ dysfunction. Clin Invest Med. 2014; 37(2):E58-69. DOI: 10.25011/cim.v37i2.21087. View

15.

Wang Y, Cao Q, Wang F, Huang L, Sang T, Liu F . SIRT1 Protects Against Oxidative Stress-Induced Endothelial Progenitor Cells Apoptosis by Inhibiting FOXO3a via FOXO3a Ubiquitination and Degradation. J Cell Physiol. 2015; 230(9):2098-107. DOI: 10.1002/jcp.24938. View

16.

Man Law I, Bakirtzi K, Polytarchou C, Oikonomopoulos A, Hommes D, Iliopoulos D . Neurotensin--regulated miR-133α is involved in proinflammatory signalling in human colonic epithelial cells and in experimental colitis. Gut. 2014; 64(7):1095-104. PMC: 4422787. DOI: 10.1136/gutjnl-2014-307329. View

17.

Abraham E, Singer M . Mechanisms of sepsis-induced organ dysfunction. Crit Care Med. 2007; 35(10):2408-16. DOI: 10.1097/01.ccm.0000282072.56245.91. View

18.

Taneja R, Parodo J, Jia S, Kapus A, Rotstein O, Marshall J . Delayed neutrophil apoptosis in sepsis is associated with maintenance of mitochondrial transmembrane potential and reduced caspase-9 activity. Crit Care Med. 2004; 32(7):1460-9. DOI: 10.1097/01.ccm.0000129975.26905.77. View

19.

Zhang W, Liu K, Liu S, Ji B, Wang Y, Liu Y . MicroRNA-133a functions as a tumor suppressor by targeting IGF-1R in hepatocellular carcinoma. Tumour Biol. 2015; 36(12):9779-88. DOI: 10.1007/s13277-015-3749-8. View

20.

Blander G, Guarente L . The Sir2 family of protein deacetylases. Annu Rev Biochem. 2004; 73:417-35. DOI: 10.1146/annurev.biochem.73.011303.073651. View