miR-20a attenuates acute lung injury in septic rats via targeting TLR4
1Department of Emergency, the First Aﬃliated Hospital of Chengdu Medical College, 610000 Chengdu, Sichuan Province, China
2Department of Anesthesiology, the First Aﬃliated Hospital of Chengdu Medical College, 610000 Chengdu, Sichuan Province, China
DOI: 10.22514/sv.2021.097 Vol.17,Issue 4,July 2021 pp.157-162
Submitted: 05 March 2021 Accepted: 12 April 2021
Published: 08 July 2021
Background: Sepsis is most likely to cause lung damage in patients, and the detection rate and mortality rate are high. Here, we investigated the expression of miR-20a in sepsis-induced acute lung injury (ALI) rats and its effect on inflammatory response, and reveal its possible molecular mechanism.
Method: The model of acute lung injury caused by sepsis in rats was established by cecal ligation and puncture. The expression of miR-20a in lung tissue was determined by RT-qPCR. Acute lung injury rats were injected with 5 nmol miR-20a agomir or agomir NC every day for 3 days. Rats were sacrificed by arterial bleeding and lung tissues were removed. Serum interleukin (IL) -1β, IL-6, and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE staining was used to observe the pathology of lung tissue and calculate the pathological score of lung injury. Western blot to determine the level of TLR4 and nuclear transcription factor κB p65 (NF-κB p65) protein in lung tissue. The luciferase reporter assay was used to verify the binding effect of miR-20a on the 3 non-coding TLR4.
Results: We found that compared with that in Normal group, the expression of miR-20a in lung tissues of rats with ALI was decreased (p < 0.05). In miR-20a agomir group, the plasma level of IL-1β, IL-6, and TNF-α was significantly lower than that in agomir NC group and ALI group (p < 0.05), while higher than those in Normal group (p < 0.05). The HE staining results showed that the pathological score of lung injury in rats in miR-20a agomir group was lower than that of agomir NC group and ALI group (p < 0.05). Compared with agomir NC group and ALI group, the expression of TLR4 and NF-κB p65 in miR-20a agomir group was decreased (p < 0.01). The luciferase reporting experiment confirmed that TLR4 was a target gene of miR-20a.
Conclusion: To sum up, miR-20a exerts a protective effect on sepsis-induced ALI rats through its anti-inflammatory effect. The targeting of TLR4 by miR-20a may be an effective method to reduce the inflammatory response in sepsis-induced ALI.
Sepsis; Acute lung injury; miR-20a; TLR4
Shuping Li,Yang Sun,Xingming Tang,Li Wang,Xiaoyuan Cheng. miR-20a attenuates acute lung injury in septic rats via targeting TLR4. Signa Vitae. 2021. 17(4);157-162.
 Xu Z, Huang Y, Mao P, Zhang J, Li Y. Sepsis and ARDS: the dark side of histones. Mediators of Inflammation. 2015; 2015: 205054.
 Zeng M, Sang W, Chen S, Chen R, Zhang H, Xue F, et al. 4-PBA inhibits LPS-induced inflammation through regulating ER stress and autophagy in acute lung injury models. Toxicology Letters. 2017; 271: 26–37.
 Li F, Chen Z, Tang H, Liang Y, Li Z, Wu J, et al. Protective effects of recombinant trichinella spiralis-53 000 protein combining with imipenem on polymicrobial septic mice. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016; 28: 433–438. (In Chinese)
 Xu C, Chong L, Yu G, Zhang H. miR-574-5p alleviates sepsis-induced acute lung injury by regulating TRAF6/NF-κB pathway. Tropical Journal of Pharmaceutical Research. 2020; 19: 676–682.
 Fu X, Qie J, Fu Q, Chen J, Jin Y, Ding Z. miR-20a-5p/TGFBR2 axis affects pro-inflammatory macrophages and aggravates liver fibrosis. Frontiers in Oncology. 2020; 10: 107.
 Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA. Immunodesign of experimental sepsis by cecal ligation and puncture. Nature Protocols. 2009; 4: 31–36.
 Council NR. Guide for the care and use of laboratory animals (pp. 246). 8th edn. Washington, DC: The National Academies Press. 2011.
 Li X, Han J, Zhu H, Peng L, Chen Z. miR‑181b‑5p mediates TGF‑β1-induced epithelial-to-mesenchymal transition in non-small cell lung cancer stem-like cells derived from lung adenocarcinoma a549 cells. International Journal of Oncology. 2017; 51: 158–168.
 Xu T, Zhou L, Shi Y, Liu L, Zuo L, Jia Q, et al. Metabolomics approach in lung tissue of septic rats and the interventional effects of Xuebijing injection using UHPLC-Q-Orbitrap-HRMS. Journal of Biochemistry. 2018; 164: 427–435.
 Le Y, Chen T, Xun K, Ding T. Expression of the long intergenic non-coding RNA (lincRNA) of the NED25 gene modulates the microRNA-125b, STAT3, nitric oxide, and procalcitonin signaling pathways in patients with sepsis. Medical Science Monitor. 2018; 24: 4555–4566.
 Jokinen E. Obesity and cardiovascular disease. Minerva Pediatrica. 2015; 67: 25–32.
 Makaryus AN, McFarlane SI. Diabetes insipidus: diagnosis and treatment of a complex disease. Cleveland Clinic Journal of Medicine. 2006; 73: 65–71.
 Mikhail FM. Copy number variations and human genetic disease. Current Opinion in Pediatrics. 2014; 26: 646–652.
 McKinnon PJ. Genome integrity and disease prevention in the nervous system. Genes & Development. 2017; 31: 1180–1194.
 Leng C, Sun J, Xin K, Ge J, Liu P, Feng X. High expression of miR-483-5p aggravates sepsis-induced acute lung injury. The Journal of Toxicological Sciences. 2020; 45: 77–86.
 Li X, Shen W, Sun Y, Li W, Sun Z, Liu Y, et al. MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes. Joint Bone Spine. 2016; 83: 695–700.
 Chen M, Li W, Zhang Y, Yang J. MicroRNA-20a protects human aortic endothelial cells from Ox-LDL-induced inflammation through targeting TLR4 and TXNIP signaling. Biomedicine & Pharmacotherapy. 2018; 103: 191–197.
 Zhu D, Pan C, Li L, Bian Z, Lv Z, Shi L, et al. MicroRNA-17/20a/106a modulate macrophage inflammatory responses through targeting signal-regulatory protein α. The Journal of Allergy and Clinical Immunology. 2013; 132: 426–436.e8.
 Qin L, Tan H, Wang Y, Xu C, Feng J, Li M, et al. Astragalus mem-branaceus and salvia miltiorrhiza ameliorate lipopolysaccharide-induced acute lung injury in rats by regulating the toll-like receptor 4/nuclear factor-kappa B signaling pathway. Evidence-Based Complementary and Alternative Medicine. 2018; 2018: 3017571.
 Liu J, Du J, Cheng X, Zhang X, Li Y, Fu X, et al. Effect of netrin-1 anti-inflammatory factor on acute lung injury in sepsis rats. Medical Science Monitor. 2019; 25: 7928–7935.
 Li J, Wang M, Song L, Wang X, Lai W, Jiang S. LncRNA MALAT1 regulates inflammatory cytokine production in lipopolysaccharide-stimulated human gingival fibroblasts through sponging miR-20a and activating TLR4 pathway. Journal of Periodontal Research. 2020; 55: 182–190.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.
IndexCopernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.
Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.
Scopus: CiteScore 0.5(2019) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.