Skip to main content
Erschienen in: Hepatology International 6/2020

10.10.2020 | Original Article

Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism

verfasst von: Yuhan Li, Yansong Luan, Jianning Li, Hui Song, Yan Li, Hi Qi, Bo Sun, Peng Zhang, Xianxian Wu, Xing Liu, Yanhui Yang, Wufan Tao, Lei Cai, Zhiwei Yang, Yi Yang

Erschienen in: Hepatology International | Ausgabe 6/2020

Einloggen, um Zugang zu erhalten

Abstract

Background and Aims

Non-alcoholic fatty liver disease (NAFLD) and its complications has become an expanding health problem worldwide with limited therapeutic approaches. The current study was aiming to identify novel microRNA in the regulation of hepatic lipid metabolism in NAFLD.

Approches and Results

Systematic screening of microRNA expression by high-throughput small RNA sequencing demonstrated that microRNA 199a-5p (miR-199a-5p) was significantly upregulated in high fat diet-induced steatosis mouse model, with the most abundant expression in adipose tissue. MST1 was further identified as the target gene for miR-199a with specific recognition at the 3′ untranslated region with dural luciferase reporter assay. Delivery of miR-199a-5p with exosomes into mice aggravated liver lipid accumulation in hepatocytes, accompanied by down-regulation of hepatic MST1 expression and modulation of hepatic lipogenesis and lipolysis, including SREBP-1c, AMPK signaling cascades and the down-stream CPT1α and FASN. Conversely, administration of exosome containing anti-miR-199a-5p resulted in attenuated steotosis in mice fed on high fat diet. Importanly, miR-199a-5p-induced abnormal cellular lipid accumulation could be markedly reversed by overexpression of MST1.

Conclusion

miR-199a-5p might be an essentail regulator for hepatic lipid metabolism, possibly through its interction with MST1 and the subsequent signaling cascade. Thus, miR-199a-5p may serve as an important therapeutic target in the treatment of NAFLD.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10:686–90.PubMedCrossRef Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10:686–90.PubMedCrossRef
2.
Zurück zum Zitat Musso G, Cassader M, Gambino R. Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies. Nat Rev Drug Discov. 2016;15:249–74.PubMedCrossRef Musso G, Cassader M, Gambino R. Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies. Nat Rev Drug Discov. 2016;15:249–74.PubMedCrossRef
3.
Zurück zum Zitat Hardy T, Mann DA. Epigenetics in liver disease: from biology to therapeutics. Gut. 2016;65:1895–905.PubMedCrossRef Hardy T, Mann DA. Epigenetics in liver disease: from biology to therapeutics. Gut. 2016;65:1895–905.PubMedCrossRef
4.
Zurück zum Zitat Stender S, Kozlitina J, Nordestgaard BG, Tybjaerg-Hansen A, Hobbs HH, Cohen JC. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nat Genet. 2017;49:842–7.PubMedPubMedCentralCrossRef Stender S, Kozlitina J, Nordestgaard BG, Tybjaerg-Hansen A, Hobbs HH, Cohen JC. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nat Genet. 2017;49:842–7.PubMedPubMedCentralCrossRef
5.
Zurück zum Zitat Zhang X, Ji X, Wang Q, Li JZ. New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Protein Cell. 2018;9:164–77.PubMedCrossRef Zhang X, Ji X, Wang Q, Li JZ. New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Protein Cell. 2018;9:164–77.PubMedCrossRef
6.
Zurück zum Zitat Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE. From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol. 2013;10:627–36.PubMedCrossRef Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE. From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol. 2013;10:627–36.PubMedCrossRef
7.
Zurück zum Zitat Korf H, van der Merwe S. Adipose-derived exosomal MicroRNAs orchestrate gene regulation in the liver: Is this the missing link in nonalcoholic fatty liver disease? Hepatology. 2017;66:1689–91.PubMedCrossRef Korf H, van der Merwe S. Adipose-derived exosomal MicroRNAs orchestrate gene regulation in the liver: Is this the missing link in nonalcoholic fatty liver disease? Hepatology. 2017;66:1689–91.PubMedCrossRef
8.
Zurück zum Zitat Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol. 2012;107:811–26.PubMedCrossRef Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol. 2012;107:811–26.PubMedCrossRef
9.
Zurück zum Zitat Ahmed A, Wong RJ, Harrison SA. Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol. 2015;13:2062–70.PubMedCrossRef Ahmed A, Wong RJ, Harrison SA. Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol. 2015;13:2062–70.PubMedCrossRef
10.
Zurück zum Zitat Monetti M, Levin MC, Watt MJ, Sajan MP, Marmor S, Hubbard BK, Stevens RD, et al. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab. 2007;6:69–78.PubMedCrossRef Monetti M, Levin MC, Watt MJ, Sajan MP, Marmor S, Hubbard BK, Stevens RD, et al. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab. 2007;6:69–78.PubMedCrossRef
11.
Zurück zum Zitat Goedeke L, Bates J, Vatner DF, Perry RJ, Wang T, Ramirez R, Li L, et al. Acetyl-CoA carboxylase inhibition reverses NAFLD and hepatic insulin resistance but promotes hypertriglyceridemia in rodents. Hepatology. 2018;68:2197–211.PubMedCrossRef Goedeke L, Bates J, Vatner DF, Perry RJ, Wang T, Ramirez R, Li L, et al. Acetyl-CoA carboxylase inhibition reverses NAFLD and hepatic insulin resistance but promotes hypertriglyceridemia in rodents. Hepatology. 2018;68:2197–211.PubMedCrossRef
12.
Zurück zum Zitat Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13:376–88.PubMedPubMedCentralCrossRef Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13:376–88.PubMedPubMedCentralCrossRef
13.
Zurück zum Zitat Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.PubMedCrossRef Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.PubMedCrossRef
15.
Zurück zum Zitat Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 2015;16:421–33.PubMedCrossRef Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 2015;16:421–33.PubMedCrossRef
16.
Zurück zum Zitat Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang WC, Li P, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature. 2015;527:100–4.PubMedPubMedCentralCrossRef Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang WC, Li P, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature. 2015;527:100–4.PubMedPubMedCentralCrossRef
17.
Zurück zum Zitat Mayourian J, Ceholski DK, Gorski PA, Mathiyalagan P, Murphy JF, Salazar SI, Stillitano F, et al. Exosomal microRNA-21-5p mediates mesenchymal stem cell paracrine effects on human cardiac tissue contractility. Circ Res. 2018;122:933–44.PubMedPubMedCentralCrossRef Mayourian J, Ceholski DK, Gorski PA, Mathiyalagan P, Murphy JF, Salazar SI, Stillitano F, et al. Exosomal microRNA-21-5p mediates mesenchymal stem cell paracrine effects on human cardiac tissue contractility. Circ Res. 2018;122:933–44.PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.CrossRefPubMed Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.CrossRefPubMed
20.
Zurück zum Zitat Wang X, Wang H, Cao J, Ye C. Exosomes from adipose-derived stem cells promotes VEGF-C-dependent lymphangiogenesis by regulating miRNA-132/TGF-beta pathway. Cell Physiol Biochem. 2018;49:160–71.PubMedCrossRef Wang X, Wang H, Cao J, Ye C. Exosomes from adipose-derived stem cells promotes VEGF-C-dependent lymphangiogenesis by regulating miRNA-132/TGF-beta pathway. Cell Physiol Biochem. 2018;49:160–71.PubMedCrossRef
21.
Zurück zum Zitat Ferrante SC, Nadler EP, Pillai DK, Hubal MJ, Wang Z, Wang JM, Gordish-Dressman H, et al. Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease. Pediatr Res. 2015;77:447–54.PubMedCrossRef Ferrante SC, Nadler EP, Pillai DK, Hubal MJ, Wang Z, Wang JM, Gordish-Dressman H, et al. Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease. Pediatr Res. 2015;77:447–54.PubMedCrossRef
22.
Zurück zum Zitat Maas SLN, Breakefield XO, Weaver AM. Extracellular vesicles: unique intercellular delivery vehicles. Trends Cell Biol. 2017;27:172–88.PubMedCrossRef Maas SLN, Breakefield XO, Weaver AM. Extracellular vesicles: unique intercellular delivery vehicles. Trends Cell Biol. 2017;27:172–88.PubMedCrossRef
23.
Zurück zum Zitat Mori MA, Raghavan P, Thomou T, Boucher J, Robida-Stubbs S, Macotela Y, Russell SJ, et al. Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metab. 2012;16:336–47.PubMedPubMedCentralCrossRef Mori MA, Raghavan P, Thomou T, Boucher J, Robida-Stubbs S, Macotela Y, Russell SJ, et al. Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metab. 2012;16:336–47.PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, et al. Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell. 2017;171(372–384):e312.CrossRef Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, et al. Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell. 2017;171(372–384):e312.CrossRef
25.
Zurück zum Zitat Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, Rao TN, et al. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017;542:450–5.PubMedPubMedCentralCrossRef Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, Rao TN, et al. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017;542:450–5.PubMedPubMedCentralCrossRef
26.
Zurück zum Zitat Kim S, Lee UJ, Kim MN, Lee EJ, Kim JY, Lee MY, Choung S, et al. MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J Biol Chem. 2008;283:18158–66.PubMedCrossRef Kim S, Lee UJ, Kim MN, Lee EJ, Kim JY, Lee MY, Choung S, et al. MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J Biol Chem. 2008;283:18158–66.PubMedCrossRef
27.
Zurück zum Zitat Shatseva T, Lee DY, Deng Z, Yang BB. MicroRNA miR-199a-3p regulates cell proliferation and survival by targeting caveolin-2. J Cell Sci. 2011;124:2826–36.PubMedCrossRef Shatseva T, Lee DY, Deng Z, Yang BB. MicroRNA miR-199a-3p regulates cell proliferation and survival by targeting caveolin-2. J Cell Sci. 2011;124:2826–36.PubMedCrossRef
28.
Zurück zum Zitat Wang Z, Ma X, Cai Q, Wang X, Yu B, Cai Q, Liu B, et al. MiR-199a-3p promotes gastric cancer progression by targeting ZHX1. FEBS Lett. 2014;588:4504–12.PubMedCrossRef Wang Z, Ma X, Cai Q, Wang X, Yu B, Cai Q, Liu B, et al. MiR-199a-3p promotes gastric cancer progression by targeting ZHX1. FEBS Lett. 2014;588:4504–12.PubMedCrossRef
29.
Zurück zum Zitat Qu Y, Huang X, Li Z, Liu J, Wu J, Chen D, Zhao F, et al. miR-199a-3p inhibits aurora kinase A and attenuates prostate cancer growth: new avenue for prostate cancer treatment. Am J Pathol. 2014;184:1541–9.PubMedCrossRef Qu Y, Huang X, Li Z, Liu J, Wu J, Chen D, Zhao F, et al. miR-199a-3p inhibits aurora kinase A and attenuates prostate cancer growth: new avenue for prostate cancer treatment. Am J Pathol. 2014;184:1541–9.PubMedCrossRef
30.
Zurück zum Zitat Ren K, Li T, Zhang W, Ren J, Li Z, Wu G. miR-199a-3p inhibits cell proliferation and induces apoptosis by targeting YAP1, suppressing Jagged1-Notch signaling in human hepatocellular carcinoma. J Biomed Sci. 2016;23:79.PubMedPubMedCentralCrossRef Ren K, Li T, Zhang W, Ren J, Li Z, Wu G. miR-199a-3p inhibits cell proliferation and induces apoptosis by targeting YAP1, suppressing Jagged1-Notch signaling in human hepatocellular carcinoma. J Biomed Sci. 2016;23:79.PubMedPubMedCentralCrossRef
31.
Zurück zum Zitat Gu N, You L, Shi C, Yang L, Pang L, Cui X, Ji C, et al. Expression of miR-199a-3p in human adipocytes is regulated by free fatty acids and adipokines. Mol Med Rep. 2016;14:1180–6.PubMedPubMedCentralCrossRef Gu N, You L, Shi C, Yang L, Pang L, Cui X, Ji C, et al. Expression of miR-199a-3p in human adipocytes is regulated by free fatty acids and adipokines. Mol Med Rep. 2016;14:1180–6.PubMedPubMedCentralCrossRef
32.
Zurück zum Zitat Zhang M, Zhang L, Hu J, Lin J, Wang T, Duan Y, Man W, et al. MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in mice. Diabetologia. 2016;59:2435–47.PubMedCrossRef Zhang M, Zhang L, Hu J, Lin J, Wang T, Duan Y, Man W, et al. MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in mice. Diabetologia. 2016;59:2435–47.PubMedCrossRef
33.
Zurück zum Zitat Geng C, Zhang Y, Gao Y, Tao W, Zhang H, Liu X, Fang F, et al. Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice. Biochem Biophys Res Commun. 2016;471:444–9.PubMedCrossRef Geng C, Zhang Y, Gao Y, Tao W, Zhang H, Liu X, Fang F, et al. Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice. Biochem Biophys Res Commun. 2016;471:444–9.PubMedCrossRef
34.
Zurück zum Zitat Ardestani A, Paroni F, Azizi Z, Kaur S, Khobragade V, Yuan T, Frogne T, et al. MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes. Nat Med. 2014;20:385–97.PubMedPubMedCentralCrossRef Ardestani A, Paroni F, Azizi Z, Kaur S, Khobragade V, Yuan T, Frogne T, et al. MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes. Nat Med. 2014;20:385–97.PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Jeong SH, Kim HB, Kim MC, Lee JM, Lee JH, Kim JH, Kim JW, et al. Hippo-mediated suppression of IRS2/AKT signaling prevents hepatic steatosis and liver cancer. J Clin Invest. 2018;128:1010–25.PubMedPubMedCentralCrossRef Jeong SH, Kim HB, Kim MC, Lee JM, Lee JH, Kim JH, Kim JW, et al. Hippo-mediated suppression of IRS2/AKT signaling prevents hepatic steatosis and liver cancer. J Clin Invest. 2018;128:1010–25.PubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Park BH, Kim DS, Won GW, Jeon HJ, Oh BC, Lee Y, Kim EG, et al. Mammalian ste20-like kinase and SAV1 promote 3T3-L1 adipocyte differentiation by activation of PPARgamma. PLoS ONE. 2012;7:e30983.PubMedPubMedCentralCrossRef Park BH, Kim DS, Won GW, Jeon HJ, Oh BC, Lee Y, Kim EG, et al. Mammalian ste20-like kinase and SAV1 promote 3T3-L1 adipocyte differentiation by activation of PPARgamma. PLoS ONE. 2012;7:e30983.PubMedPubMedCentralCrossRef
37.
Zurück zum Zitat Nascimbeni F, Bedossa P, Fedchuk L, Pais R, Charlotte F, Lebray P, Poynard T, et al. Clinical validation of the FLIP algorithm and the SAF score in patients with non-alcoholic fatty liver disease. J Hepatol. 2020;72:828–38.PubMedCrossRef Nascimbeni F, Bedossa P, Fedchuk L, Pais R, Charlotte F, Lebray P, Poynard T, et al. Clinical validation of the FLIP algorithm and the SAF score in patients with non-alcoholic fatty liver disease. J Hepatol. 2020;72:828–38.PubMedCrossRef
38.
Zurück zum Zitat Bedossa P, Consortium FP (2014) Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 60:565–575 Bedossa P, Consortium FP (2014) Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 60:565–575
39.
Zurück zum Zitat Murakami Y, Toyoda H, Tanaka M, Kuroda M, Harada Y, Matsuda F, Tajima A, et al. The progression of liver fibrosis is related with overexpression of the miR-199 and 200 families. PLoS ONE. 2011;6:e16081.PubMedPubMedCentralCrossRef Murakami Y, Toyoda H, Tanaka M, Kuroda M, Harada Y, Matsuda F, Tajima A, et al. The progression of liver fibrosis is related with overexpression of the miR-199 and 200 families. PLoS ONE. 2011;6:e16081.PubMedPubMedCentralCrossRef
40.
Zurück zum Zitat Yang X, Ma L, Wei R, Ye T, Zhou J, Wen M, Men R, et al. Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-beta pathway. Signal Transduct Target Ther. 2020;5:75.PubMedPubMedCentralCrossRef Yang X, Ma L, Wei R, Ye T, Zhou J, Wen M, Men R, et al. Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-beta pathway. Signal Transduct Target Ther. 2020;5:75.PubMedPubMedCentralCrossRef
41.
Zurück zum Zitat Li B, Zhang Z, Zhang H, Quan K, Lu Y, Cai D, Ning G. Aberrant miR199a-5p/caveolin1/PPARalpha axis in hepatic steatosis. J Mol Endocrinol. 2014;53:393–403.PubMedCrossRef Li B, Zhang Z, Zhang H, Quan K, Lu Y, Cai D, Ning G. Aberrant miR199a-5p/caveolin1/PPARalpha axis in hepatic steatosis. J Mol Endocrinol. 2014;53:393–403.PubMedCrossRef
42.
Zurück zum Zitat Deng ZB, Poliakov A, Hardy RW, Clements R, Liu C, Liu Y, Wang J, et al. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes. 2009;58:2498–505.PubMedPubMedCentralCrossRef Deng ZB, Poliakov A, Hardy RW, Clements R, Liu C, Liu Y, Wang J, et al. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes. 2009;58:2498–505.PubMedPubMedCentralCrossRef
43.
Zurück zum Zitat Allaire M, Rautou PE, Codogno P, Lotersztajn S. Autophagy in liver diseases: time for translation? J Hepatol. 2019;70:985–98.PubMedCrossRef Allaire M, Rautou PE, Codogno P, Lotersztajn S. Autophagy in liver diseases: time for translation? J Hepatol. 2019;70:985–98.PubMedCrossRef
44.
Zurück zum Zitat Kanda T, Matsuoka S, Yamazaki M, Shibata T, Nirei K, Takahashi H, Kaneko T, et al. Apoptosis and non-alcoholic fatty liver diseases. World J Gastroenterol. 2018;24:2661–722.PubMedPubMedCentralCrossRef Kanda T, Matsuoka S, Yamazaki M, Shibata T, Nirei K, Takahashi H, Kaneko T, et al. Apoptosis and non-alcoholic fatty liver diseases. World J Gastroenterol. 2018;24:2661–722.PubMedPubMedCentralCrossRef
45.
Zurück zum Zitat Arab JP, Arrese M, Trauner M. Recent insights into the pathogenesis of nonalcoholic fatty liver disease. Annu Rev Pathol. 2018;13:321–50.PubMedCrossRef Arab JP, Arrese M, Trauner M. Recent insights into the pathogenesis of nonalcoholic fatty liver disease. Annu Rev Pathol. 2018;13:321–50.PubMedCrossRef
46.
Zurück zum Zitat Song T, Zhang X, Yang G, Song Y, Cai W. Decrement of miR-199a-5p contributes to the tumorigenesis of bladder urothelial carcinoma by regulating MLK3/NF-kappaB pathway. Am J Transl Res. 2015;7:2786–94.PubMedPubMedCentral Song T, Zhang X, Yang G, Song Y, Cai W. Decrement of miR-199a-5p contributes to the tumorigenesis of bladder urothelial carcinoma by regulating MLK3/NF-kappaB pathway. Am J Transl Res. 2015;7:2786–94.PubMedPubMedCentral
47.
Zurück zum Zitat Li Z, Song Y, Liu L, Hou N, An X, Zhan D, Li Y, et al. miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation. Cell Death Differ. 2017;24:1205–13.PubMedCrossRef Li Z, Song Y, Liu L, Hou N, An X, Zhan D, Li Y, et al. miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation. Cell Death Differ. 2017;24:1205–13.PubMedCrossRef
48.
Zurück zum Zitat Lou G, Song X, Yang F, Wu S, Wang J, Chen Z, Liu Y. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 2015;8:122.PubMedPubMedCentralCrossRef Lou G, Song X, Yang F, Wu S, Wang J, Chen Z, Liu Y. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 2015;8:122.PubMedPubMedCentralCrossRef
49.
Zurück zum Zitat Wang F, Li L, Piontek K, Sakaguchi M, Selaru FM. Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma. Hepatology. 2018;67:940–54.PubMedCrossRef Wang F, Li L, Piontek K, Sakaguchi M, Selaru FM. Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma. Hepatology. 2018;67:940–54.PubMedCrossRef
50.
Zurück zum Zitat Vega-Badillo J, Gutierrez-Vidal R, Hernandez-Perez HA, Villamil-Ramirez H, Leon-Mimila P, Sanchez-Munoz F, Moran-Ramos S, et al. Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects. Liver Int. 2016;36:1383–91.PubMedCrossRef Vega-Badillo J, Gutierrez-Vidal R, Hernandez-Perez HA, Villamil-Ramirez H, Leon-Mimila P, Sanchez-Munoz F, Moran-Ramos S, et al. Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects. Liver Int. 2016;36:1383–91.PubMedCrossRef
51.
Metadaten
Titel
Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism
verfasst von
Yuhan Li
Yansong Luan
Jianning Li
Hui Song
Yan Li
Hi Qi
Bo Sun
Peng Zhang
Xianxian Wu
Xing Liu
Yanhui Yang
Wufan Tao
Lei Cai
Zhiwei Yang
Yi Yang
Publikationsdatum
10.10.2020
Verlag
Springer India
Erschienen in
Hepatology International / Ausgabe 6/2020
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-020-10096-0

Weitere Artikel der Ausgabe 6/2020

Hepatology International 6/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.