Augmenter of liver regeneration enhances cell proliferation through the microRNA-26a/Akt/cyclin D1 pathway in hepatic cells.
augmenter of liver regeneration
microRNA-26a
phosphatase and tensin homolog
proliferation
regeneration
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
14
12
2018
revised:
23
04
2019
accepted:
28
06
2019
pubmed:
4
7
2019
medline:
4
7
2019
entrez:
4
7
2019
Statut:
ppublish
Résumé
Hepatocytes can proliferate and regenerate when injured by toxins, viral infections, and so on. Augmenter of liver regeneration (ALR) is a key regulator of liver regeneration, but the mechanism is unknown. The role of ALR in other cell types is not known. In the present study, we investigated the relationship between microRNA (miRNA)-26a and ALR in the Huh7 cell line and adipose tissue-derived mesenchymal cells from chronic liver disease patients and healthy individuals. Huh7 cells were transfected independently with ALR and miRNA-26a expression vectors, and their effects on cell proliferation, the expression of miRNA-26a, and activation of the phosphatase and tensin homolog and Akt signaling pathways were determined. The experiments were repeated on mesenchymal stem cells derived from healthy individuals and chronic liver disease patients to see whether the observations can be replicated in primary cells. Overexpression of ALR or miRNA-26a resulted in an increase of the phosphorylation of Akt and cyclin D1 expression, whereas it resulted in decreased levels of p-GSK-3β and phosphatase and tensin homolog in Huh7 cells. The inhibition of ALR expression by ALR siRNA or anti-miR-26a decreased the Akt/cyclin D1 signaling pathway, leading to decreased proliferation. Mesenchymal stem cells isolated from the chronic liver disease patients had a higher ALR expression, while the mesenchymal stem cells isolated from healthy volunteers responded to the growth factor treatments for increased ALR expression. It was found that there was a significant increase in miRNA-26a expression and proliferation. These data clearly showed that ALR induced the expression of miRNA-26a, which downregulated phosphatase and tensin homolog, resulting in an increased p-Akt/cyclin D1 pathway and enhanced proliferation in hepatic cells.
Types de publication
Journal Article
Langues
eng
Pagination
1341-1352Subventions
Organisme : Department of Science and Technology, Ministry of Science and Technology
Organisme : University Grants Commission
Informations de copyright
© 2019 The Japan Society of Hepatology.
Références
Gupta P, Venugopal SK. Augmenter of liver regeneration: A key protein in liver regeneration and pathophysiology. Hepatol Res 2018 Jul; 48: 587-596.
Ilowski M, Putz C, Weiss TS et al. Augmenter of liver regeneration causes different kinetics of ERK1/2 and Akt/PKB phosphorylation than EGF and induces hepatocyte proliferation in an EGF receptor independent and liver specific manner. Biochem Biophys Res Commun 2010 Apr 16; 394: 915-920.
Huang LL, Long RT, Jiang GP et al. Augmenter of liver regeneration promotes mitochondrial biogenesis in renal ischemia-reperfusion injury. Apoptosis 2018 Dec; 23: 695-706.
Pu T, Liao XH, Sun H et al. Augmenter of liver regeneration regulates autophagy in renal ischemia-reperfusion injury via the AMPK/mTOR pathway. Apoptosis 2017 Jul; 22: 955-969.
Gandhi CR, Chaillet JR, Nalesnik MA et al. Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice. Gastroenterology 2015 Feb; 148: 379-91 e4.
Zeng HQ, Luo Y, Lou SF, Liu Q, Zhang L, Deng JC. Silencing of augmenter of liver regeneration inhibited cell proliferation and triggered apoptosis in U266 human multiple myeloma cells. Braz J Med Biol Res 2017 Aug 31; 50: e6139.
Kumar S, Wang J, Rani R, Gandhi CR. Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice. PLoS ONE 2016; 11: e0147864.
Pant K, Venugopal SK. Circulating microRNAs: Possible role as non-invasive diagnostic biomarkers in liver disease. Clin Res Hepatol Gastroenterol 2017 Sep; 41: 370-377.
Yoon S, Kim TH, Natarajan A et al. Acute liver injury upregulates microRNA-491-5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-alpha-induced apoptosis. Liver Int 2010 Mar; 30: 376-387.
Lin X, Chen L, Li H et al. miR-155 accelerates proliferation of mouse hepatocytes during liver regeneration by directly targeting SOCS1. Am J Physiol Gastrointest Liver Physiol 2018 Oct 1; 315: G443-G453.
Lan X, Li G, Liu H, Fu H, Chen P, Liu M. MiR-27a/b Regulates Liver Regeneration by Posttranscriptional Modification of Tmub1. Dig Dis Sci 2018 Sep; 63: 2362-2372.
Liu B, Wu X, Liu B et al. MiR-26a enhances metastasis potential of lung cancer cells via AKT pathway by targeting PTEN. Biochim Biophys Acta 2012 Nov; 1822: 1692-1704.
Qian X, Zhao P, Li W et al. MicroRNA-26a promotes tumor growth and angiogenesis in glioma by directly targeting prohibitin. CNS Neurosci Ther 2013 Oct; 19: 804-812.
Qu F, Li CB, Yuan BT et al. MicroRNA-26a induces osteosarcoma cell growth and metastasis via the Wnt/beta-catenin pathway. Oncol Lett 2016 Feb; 11: 1592-1596.
Salvatori B, Iosue I, Mangiavacchi A et al. The microRNA-26a target E2F7 sustains cell proliferation and inhibits monocytic differentiation of acute myeloid leukemia cells. Cell Death Dis 2012 Oct 25; 3: e413.
Zhang J, Han C, Wu T. MicroRNA-26a promotes cholangiocarcinoma growth by activating beta-catenin. Gastroenterology 2012 Jul; 143: 246-56 e8.
Zhang Y, Zhao Y, Wu J, Liangpunsakul S, Niu J, Wang L. MicroRNA-26-5p functions as a new inhibitor of hepatoblastoma by repressing lin-28 homolog B and aurora kinase a expression. Hepatol Commun 2018 Jul; 2: 861-871.
Pant K, Yadav AK, Gupta P, Islam R, Saraya A, Venugopal SK. Butyrate induces ROS-mediated apoptosis by modulating miR-22/SIRT-1 pathway in hepatic cancer cells. Redox Biol 2017 Aug; 12: 340-349.
Thirunavukkarasu C, Wang LF, Harvey SA et al. Augmenter of liver regeneration: an important intracellular survival factor for hepatocytes. J Hepatol 2008 Apr; 48: 578-588.
Michalopoulos GK. Liver regeneration. J Cell Physiol 2007 Nov; 213: 286-300.
Cienfuegos JA, Rotellar F, Baixauli J, Martinez-Regueira F, Pardo F, Hernandez-Lizoain JL. Liver regeneration--the best kept secret. A model of tissue injury response. Rev Esp Enferm Dig 2014 Mar; 106: 171-194.
Dayoub R, Groitl P, Dobner T, Bosserhoff AK, Schlitt HJ, Weiss TS. Foxa2 (HNF-3beta) regulates expression of hepatotrophic factor ALR in liver cells. Biochem Biophys Res Commun 2010 May 14; 395: 465-470.
Dong LY, Sun G, Jiang L et al. Epidermal growth factor down-regulates the expression of human hepatic stimulator substance via CCAAT/enhancer-binding protein beta in HepG2 cells. Biochem J 2010 Oct 15; 431: 277-287.
Hagiya M, Francavilla A, Polimeno L et al. Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution. Proc Natl Acad Sci U S A 1994 Aug 16; 91: 8142-8146.
Song M, Yi X, Chen W et al. Augmenter of liver regeneration (ALR) gene therapy attenuates CCl4-induced liver injury and fibrosis in rats. Biochem Biophys Res Commun 2011; 415: 152-156.
Shi H, Han W, Shi H et al. Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting autophagy in mice. Oncotarget 2017 Feb 21; 8: 12637-12648.
Francavilla A, Pesetti B, Barone M et al. Transient GFER knockdown in vivo impairs liver regeneration after partial hepatectomy. Int J Biochem Cell Biol 2014 Aug; 53: 343-351.
Yang K, Du C, Cheng Y, Li Y, Gong J, Liu Z. Augmenter of liver regeneration promotes hepatic regeneration depending on the integrity of Kupffer cell in rat small-for-size liver transplantation. J Surg Res 2013 Aug; 183: 922-928.
Pant K, Saraya A, Venugopal SK. Oxidative stress plays a key role in butyrate-mediated autophagy via Akt/mTOR pathway in hepatoma cells. Chem Biol Interact 2017 Aug 1; 273: 99-106.
Farina FM, Inguscio A, Kunderfranco P, Cortesi A, Elia L, Quintavalle M. MicroRNA-26a/cyclin-dependent kinase 5 axis controls proliferation, apoptosis and in vivo tumor growth of diffuse large B-cell lymphoma cell lines. Cell Death Dis 2017 Jun 22; 8: e2890.
Ma Y, Deng F, Li P, Chen G, Tao Y, Wang H. The tumor suppressive miR-26a regulation of FBXO11 inhibits proliferation, migration and invasion of hepatocellular carcinoma cells. Biomed Pharmacother 2018 May; 101: 648-655.
Chen J, Zhang K, Xu Y et al. The role of microRNA-26a in human cancer progression and clinical application. Tumour Biol 2016 Jun; 37: 7095-7108.
Sawitza I, Kordes C, Gotze S, Herebian D, Haussinger D. Bile acids induce hepatic differentiation of mesenchymal stem cells. Sci Rep 2015 Aug 25; 5: 13320.
Raut A, Khanna A. High-throughput sequencing to identify microRNA signatures during hepatic differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells. Hepatol Res 2017 Aug; 47: 910-927.
Wu Q, Tang J, Li Y et al. Hepatic differentiation of mouse bone marrowderived mesenchymal stem cells using a novel 3D culture system. Mol Med Rep 2017 Dec; 16: 9473-9479.
Wang N, Wang Z, Sun H, Shi X, Zhang Y, Liu Q. Augmenter of liver regeneration improves therapeutic effect of hepatocyte homotransplantation in acute liver failure rats. Int Immunopharmacol 2013 Feb; 15: 325-332.
Li Y, Farooq M, Sheng D et al. Augmenter of liver regeneration (alr) promotes liver outgrowth during zebrafish hepatogenesis. PLoS ONE 2012; 7: e30835.
Dayoub R, Wagner H, Bataille F et al. Liver regeneration associated protein (ALR) exhibits antimetastatic potential in hepatocellular carcinoma. Mol Med 2011 Mar-Apr; 17: 221-228.