2019, Number 1
<< Back Next >>
Ann Hepatol 2019; 18 (1)
miR-182-5p Attenuates High-Fat -Diet-Induced Nonalcoholic Steatohepatitis in Mice
Liang Q, Chen H, Xu X, Jiang W
Language: English
References: 26
Page: 116-125
PDF size: 703.17 Kb.
ABSTRACT
Introduction and aim. Patients with NASH have increased risk for sepsis or cardiovascular disease after Liver transplantation.
An important role of Toll-like receptor (TLR) 4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) was demonstrated. Here,
we study the role of miR-182-5p in TLR4 expression and high-fat-diet (HFD)-induced NASH
in vitro and
in vivo.
Material and
methods. Following transfection with a miR-182-5p mimic, the effect of miR-182-5p on TLR4 in RAW264.7 and HepG2 cells was
investigated. Following administration of the miR-182-5p mimic into the livers of HFD-induced NASH mice, we determined the
in vivo
expression of TLR4, TNFα, and IL-6 and assessed the histologic features of the livers.
Results. Following lipopolysaccharide
(LPS) treatment of RAW264.7 cells, real-time RT-PCR and western blot results indicated decreases levels of TLR4 mRNA and protein
in the miR-182-5p group as compared with levels observed in controls, with similar trends were observed in TNFα and IL-6 protein
levels. Following oleic acid (OA) treatment of HepG2 cells, TLR4, TNFα, and IL-6 levels were significantly decreased in the
miR-182-5p group as compared with levels observed in controls. Following miR-182-5p administration, TLR4 mRNA and protein levels
decreased along with those of TNFα and IL-6 proteins, and the liver weight/body weight ratio of treated mice was less than that
observed in controls. Furthermore, hematoxylin and eosin staining showed that the miR-182-5p-treated group exhibited low adiposecell
cross-sectional areas, and Oil Red O staining showed decreases in the size of lipid droplets in the miR-182-5p-treated group.
Conclusions. miR-182-5p ameliorated HFD-induced NASH by suppressing TLR4.
REFERENCES
Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA 2015; 313: 2263-73.
Targher G, Chonchol MB, Byrne CD. CKD and nonalcoholic fatty liver disease. Am J Kidney Dis 2014; 64: 638-52.
Granér M, Nyman K, Siren R, Pentikäinen MO, Lundbom J, Hakkarainen A, Lauerma K, et al. Ectopic fat depots and left ventricular function in non-diabetic men with nonalcoholic fatty liver disease. Circ Cardiovasc Imaging 2015; 8: e001979.
Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998; 114: 842-5.
Day CP. From fat to inflammation. Gastroenterology 2006; 130: 207-10.
Rivera CA, Adegboyega P, van Rooijen N, Tagalicud A, Allman M, Wallace M. Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis. J Hepatol 2007; 47: 571-9.
Spruss A, Kanuri G, Wagnerberger S, Haub S, Bischoff SC, Bergheim I. Toll-Like Receptor 4 Is Involved in the Development of Fructose-Induced Hepatic Steatosis in Mice. Hepatology 2009; 50: 1094-104.
Li L, Chen L, Hu L, Liu Y, Sun HY, Tang J, Hou YJ, et al. Nuclear Factor High-Mobility Group Box1 Mediating the Activation of Toll-Like Receptor 4 Signaling in Hepatocytes in the Early Stage of Nonalcoholic Fatty Liver Disease in Mice. Hepatology 2011; 54: 1620-30.
Chen W, Wang X, Huang LI, Liu BO. Hepcidin in non-alcoholic fatty liver disease regulated by the TLR4/NF-kB signaling pathway. Exp Ther Med 2016; 11: 73-6.
Takeda K, Akira S. TLR signaling pathways. Semin Immunol 2004; 16: 329.
Seki E, Brenner DA. Toll-like receptors and adaptor molecules in liver disease: update. Hepatology 2008; 48: 322-35.
Akira S, Takeda K. Toll-like receptor signaling. Nat Rev Immunol 2004; 4: 499-511.
Ambros V. The functions of animal microRNAs. Nature 2004; 431: 350-5.
Jiang W, Kong L, Ni Q, Lu Y, Ding W, Liu G, Pu L, et al. miR- 146a ameliorates liver ischemia/reperfusion injury by suppressing IRAK1 and TRAF6. PLoS One 2014; 9: e101530.
Jiang W, Ni Q, Tan L, Kong L, Lu Y, Xu X, Kong L. The microRNA- 146a/b attenuates acute small-for-size liver graft injury in rats. Liver Int 2015; 35: 914-24.
Jiang W, Hu M, Rao J, Xu X, Wang X, Kong L. Over-expression of Toll-like receptors and their ligands in small-for-size graft. Hepatol Res 2010; 40: 318-29.
Jiang W, Liu J, Dai Y, Zhou N, Ji C, Li X. MiR-146b attenuates high-fat diet-induced non-alcoholic steatohepatitis in mice. J Gastroenterol Hepatol 2015; 30: 933-43.
Jiang W, Liu G, Tang W. MicroRNA-182-5p Ameliorates Liver Ischemia-Reperfusion Injury by Suppressing Toll-Like Receptor 4. Transplant Proc 2016; 48: 2809-14.
Qin SB, Peng DY, Shi Y, Ke ZP. MiR-182-5p Inhibited Oxidative Stress and Apoptosis Triggered by Oxidized Low-Density Lipoprotein via Targeting Toll-Like Receptor 4. J Cell Physiol 2017 [Epub ahead of print].
Xu S,Witmer PD, Lumayag S, Kovacs B, Valle D. MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. J Biol Chem 2007; 282: 25053-66.
Li H, Kloosterman W, Fekete DM. MicroRNA-183 family members regulate sensorineural fates in the inner ear. J Neurosci 2010; 30: 3254-63.
Guttilla IK,White BA. Coordinate regulation of FOXO1 by miR- 27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem 2009; 284: 23204-16.
Chiang CH, Hou MF, HungWC. Up-regulation of miR-182 by âcatenin in breast cancer increases tumorigenicity andinvasiveness by targeting the matrix metalloproteinase inhibitor RECK. Biochim Biophys Acta 2013; 1830: 3067-76.
Rasheed SA, Teo CR, Beillard EJ, Voorhoeve PM, Casey PJ. MicroRNA-182 and microRNA-200a control G-protein subunit alpha-13 (GNA13) expression and cell invasion synergistically in prostate cancer cells. J Biol Chem 2013; 288: 7986-95.
Li Y, Chen S, Shan Z, Bi L, Yu S, Li Y, Xu S. miR-182-5p improves the viability, mitosis, migration, and invasion ability of human gastric cancer cells by down-regulating RAB27A. Biosci Rep 2017; 37: pii: BSR20170136.
Zhou X, Zhang C, Zhang C, Peng Y, Wang Y, Xu H. MicroRNA- 182-5p Regulates Nerve Injury-induced Nociceptive Hypersensitivity by Targeting Ephrin Type-b Receptor 1. Anesthesiology 2017; 126: 967-77.