{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T07:45:14Z","timestamp":1794123914682,"version":"4.8.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Nonalcoholic fatty liver disease (NAFLD) has emerged globally and is associated with inflammatory signaling. The underlying mechanisms remain poorly delineated, although NAFLD has attracted considerable attention and been extensively investigated. Recent publications have determined that angiotensin II (Ang II) plays an important role in stimulating NAFLD progression by causing lipid metabolism disorder and insulin resistance through its main receptor, Ang II type 1 receptor (AT1R). Herein, we explored the effect of supplementary\n                    <jats:italic>S<\/jats:italic>\n                    -adenosylmethionine (SAM), which is the main biological methyl donor in mammalian cells, in regulating AT1R-associated protein (ATRAP), which is the negative regulator of AT1R. We found that SAM was depleted in NAFLD and that SAM supplementation ameliorated steatosis. In addition, in both high-fat diet-fed C57BL\/6 rats and L02 cells treated with oleic acid (OA), ATRAP expression was downregulated at lower SAM concentrations. Mechanistically, we found that the subcellular localization of human antigen R (HuR) was determined by the SAM concentration due to protein methylation modification. Moreover, HuR was demonstrated to directly bind ATRAP mRNA and control its nucleocytoplasmic shuttling. Thus, SAM was suggested to upregulate ATRAP protein expression by maintaining the export of its mRNA from the nucleus. Taken together, our findings suggest that SAM can positively regulate ATRAP in NAFLD and may have various potential benefits for the treatment of NAFLD.\n                  <\/jats:p>","DOI":"10.1038\/s41419-021-03591-1","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T03:03:09Z","timestamp":1616382189000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["S-adenosylmethionine upregulates the angiotensin receptor-binding protein ATRAP via the methylation of HuR in NAFLD"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7340-3762","authenticated-orcid":false,"given":"Tao","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyue-Fang","family":"Battaglia-Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9101-0364","authenticated-orcid":false,"given":"Zhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"3591_CR1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.5114\/ceji.2018.77395","volume":"43","author":"M Kosmalski","year":"2018","unstructured":"Kosmalski, M., Mokros, \u0141., Kuna, P., Witusik, A. & Pietras, T. Changes in the immune system - the key to diagnostics and therapy of patients with non-alcoholic fatty liver disease. Cent. Eur. J. Immunol. 43, 231\u2013239 (2018).","journal-title":"Cent. Eur. J. Immunol."},{"key":"3591_CR2","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1016\/j.ultrasmedbio.2018.07.019","volume":"44","author":"A Ozturk","year":"2018","unstructured":"Ozturk, A. et al. Quantitative hepatic fat quantification in non-alcoholic fatty liver disease using ultrasound-based techniques: a review of literature and their diagnostic performance. Ultrasound Med. Biol. 44, 2461\u20132475 (2018).","journal-title":"Ultrasound Med. Biol."},{"key":"3591_CR3","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1002\/hep.23119","volume":"50","author":"R Loomba","year":"2009","unstructured":"Loomba, R., Sirlin, C. B., Schwimmer, J. B. & Lavine, J. E. Advances in pediatric nonalcoholic fatty liver disease. Hepatology 50, 1282\u20131293 (2009).","journal-title":"Hepatology"},{"key":"3591_CR4","doi-asserted-by":"publisher","first-page":"S412","DOI":"10.1194\/jlr.R800089-JLR200","volume":"50","author":"SK Erickson","year":"2009","unstructured":"Erickson, S. K. Nonalcoholic fatty liver disease. J. Lipid Res. 50, S412\u2013S416 (2009).","journal-title":"J. Lipid Res."},{"key":"3591_CR5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11894-008-0011-1","volume":"10","author":"W Dunn","year":"2008","unstructured":"Dunn, W. & Schwimmer, J. B. The obesity epidemic and nonalcoholic fatty liver disease in children. Curr. Gastroenterol. Rep. 10, 67\u201372 (2008).","journal-title":"Curr. Gastroenterol. Rep."},{"key":"3591_CR6","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1056\/NEJMra011775","volume":"346","author":"P Angulo","year":"2002","unstructured":"Angulo, P. Nonalcoholic fatty liver disease. N. Engl. J. Med. 346, 1221\u20131231 (2002).","journal-title":"N. Engl. J. Med."},{"key":"3591_CR7","doi-asserted-by":"publisher","first-page":"S47","DOI":"10.1016\/j.jhep.2014.12.012","volume":"62","author":"CD Byrne","year":"2015","unstructured":"Byrne, C. D. & Targher, G. NAFLD: a multisystem disease. J. Hepatol. 62, S47\u2013S64 (2015).","journal-title":"J. Hepatol."},{"key":"3591_CR8","first-page":"358","volume":"15","author":"JE Toblli","year":"2002","unstructured":"Toblli, J. E., Ferder, L., Stella, I., Angerosa, M. & Inserra, F. Enalapril prevents fatty liver in nephrotic rats. J. Nephrol. 15, 358\u2013367 (2002).","journal-title":"J. Nephrol."},{"key":"3591_CR9","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1089\/ars.2005.7.1346","volume":"7","author":"R Bataller","year":"2005","unstructured":"Bataller, R., Sancho-Bru, P., Gin\u00e8s, P. & Brenner, D. A. Liver fibrogenesis: a new role for the renin-angiotensin system. Antioxid. Redox Signal. 7, 1346\u20131355 (2005).","journal-title":"Antioxid. Redox Signal."},{"key":"3591_CR10","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1002\/hep.20420","volume":"40","author":"S Yokohama","year":"2004","unstructured":"Yokohama, S. et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 40, 1222\u20131225 (2004).","journal-title":"Hepatology"},{"key":"3591_CR11","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s41440-018-0040-6","volume":"41","author":"MA Luciana","year":"2018","unstructured":"Luciana, M. A., Jo\u00e3o, F. R., Igor, V., Deborah, F. & Sergio, H. S. The role of the angiotensin II type I receptor blocker telmisartan in the treatment of non-alcoholic fatty liver disease: a brief review. Hypertens. Res. 41, 394\u2013405 (2018).","journal-title":"Hypertens. Res."},{"key":"3591_CR12","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/oby.2007.114","volume":"16","author":"E Jorge","year":"2008","unstructured":"Jorge, E. et al. ACE inhibition and AT1 receptor blockade prevent fatty liver and fibrosis in obese Zucker rats. Obesity 16, 770\u2013776 (2008).","journal-title":"Obesity"},{"key":"3591_CR13","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.yjmcc.2014.12.007","volume":"79","author":"N Li","year":"2015","unstructured":"Li, N. et al. Activation of the cardiac proteasome promotes angiotension II-induced hypertrophy by down-regulation of ATRAP. J. Mol. Cell. Cardiol. 79, 303\u2013314 (2015).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"3591_CR14","doi-asserted-by":"publisher","first-page":"5038","DOI":"10.1091\/mbc.e03-06-0383","volume":"14","author":"M Lopez-Ilasaca","year":"2003","unstructured":"Lopez-Ilasaca, M., Liu, X., Tamura, K. & Dzau, V. J. The angiotensin II type I receptor-associated protein, ATRAP, is a transmembrane protein and a modulator of angiotensin II signaling. Mol. Biol. Cell 14, 5038\u20135050 (2003).","journal-title":"Mol. Biol. Cell"},{"key":"3591_CR15","doi-asserted-by":"publisher","first-page":"17058","DOI":"10.1074\/jbc.274.24.17058","volume":"274","author":"L Daviet","year":"1999","unstructured":"Daviet, L. et al. Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor. J. Biol. Chem. 274, 17058\u201317062 (1999).","journal-title":"J. Biol. Chem."},{"key":"3591_CR16","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1016\/j.febslet.2005.01.068","volume":"579","author":"Y Tanaka","year":"2005","unstructured":"Tanaka, Y. et al. The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy. FEBS Lett. 579, 1579\u20131586 (2005).","journal-title":"FEBS Lett."},{"key":"3591_CR17","doi-asserted-by":"publisher","first-page":"e000312","DOI":"10.1161\/JAHA.113.000312","volume":"2","author":"A Maeda","year":"2013","unstructured":"Maeda, A. et al. Angiotensin receptor-binding protein ATRAP\/Agtrap inhibits metabolic dysfunction with visceral obesity. J. Am. Heart Assoc. 2, e000312 (2013).","journal-title":"J. Am. Heart Assoc."},{"key":"3591_CR18","doi-asserted-by":"publisher","first-page":"3763","DOI":"10.3892\/mmr.2015.3849","volume":"12","author":"H Huang","year":"2015","unstructured":"Huang, H., Zhou, J., Cui, Z., Wang, B. & Hu, Y. Angiotensin II type 1 receptor-associated protein plays a role in regulating the local renin-angiotensin system in HSC-T6 cells. Mol. Med. Rep. 12, 3763\u20133768 (2015).","journal-title":"Mol. Med. Rep."},{"key":"3591_CR19","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S1665-2681(19)31355-9","volume":"12","author":"JM Mato","year":"2013","unstructured":"Mato, J. M., Mart\u00ednez-Chantar, M. L. & Lu, S. C. S-adenosylmethionine metabolism and liver disease. Ann. Hepatol. 12, 183\u2013189 (2013).","journal-title":"Ann. Hepatol."},{"key":"3591_CR20","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1152\/physrev.00047.2011","volume":"92","author":"SC Lu","year":"2012","unstructured":"Lu, S. C. & Mato, J. M. S-adenosylmethionine in liver health, injury, and cancer. Physiol. Rev. 92, 1515\u20131542 (2012).","journal-title":"Physiol. Rev."},{"key":"3591_CR21","doi-asserted-by":"publisher","first-page":"3849","DOI":"10.1158\/0008-5472.CAN-17-3833","volume":"78","author":"T Guo","year":"2018","unstructured":"Guo, T. et al. SNHG6 acts as a genome-wide hypomethylation trigger via coupling of miR-1297-mediated S-adenosylmethionine-dependent positive feedback loops. Cancer Res. 78, 3849\u20133864 (2018).","journal-title":"Cancer Res."},{"key":"3591_CR22","doi-asserted-by":"publisher","first-page":"e0122124","DOI":"10.1371\/journal.pone.0122124","volume":"10","author":"T Guo","year":"2015","unstructured":"Guo, T., Chang, L., Xiao, Y. & Liu, Q. S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis. PLoS ONE 10, e0122124 (2015).","journal-title":"PLoS ONE"},{"key":"3591_CR23","doi-asserted-by":"publisher","first-page":"1151S","DOI":"10.1093\/ajcn\/76.5.1151S","volume":"76","author":"T Bottiglieri","year":"2002","unstructured":"Bottiglieri, T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside\u2013molecular basis of a pleiotrophic molecule. Am. J. Clin. Nutr. 76, 1151S\u20131157S (2002).","journal-title":"Am. J. Clin. Nutr."},{"key":"3591_CR24","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1177\/1535370215579161","volume":"240","author":"M Noureddin","year":"2015","unstructured":"Noureddin, M., Mato, J. M. & Lu, S. C. Nonalcoholic fatty liver disease: update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine. Exp. Biol. Med. 240, 809\u2013820 (2015).","journal-title":"Exp. Biol. Med."},{"key":"3591_CR25","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/jbt.20109","volume":"20","author":"HS Oz","year":"2006","unstructured":"Oz, H. S., Im, H. J., Chen, T. S., Villiers, W. J. & McClain, C. J. Glutathione-enhancing agents protect against steatohepatitis in a dietary model. J. Biochem. Mol. Toxicol. 20, 39\u201347 (2006).","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"3591_CR26","first-page":"31","volume":"273","author":"A Antoniv","year":"2017","unstructured":"Antoniv, A., Antofiychuk, N., Danylyshina, T., Trefanenko, I. & Shuper, V. Clinical efficacy of S-adenosylmethionine in patients with non-alcoholic steatohepatitis and chronic kidney disease I-II stage. Georgian Med. News 273, 31\u201336 (2017).","journal-title":"Georgian Med. News"},{"key":"3591_CR27","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.bbr.2019.02.011","volume":"364","author":"T Sandra","year":"2019","unstructured":"Sandra, T. et al. Behavioral and metabolic effects of S-adenosylmethionine and imipramine in the flinders sensitive line rat model of depression. Behav. Brain Res. 364, 274\u2013280 (2019).","journal-title":"Behav. Brain Res."},{"key":"3591_CR28","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.lfs.2016.06.001","volume":"157","author":"C Xie","year":"2016","unstructured":"Xie, C. et al. Dihydromyricetin ameliorates oleic acid-induced lipid accumulation in L02 and HepG2 cells by inhibiting lipogenesis and oxidative stress. Life Sci. 157, 131\u2013139 (2016).","journal-title":"Life Sci."},{"key":"3591_CR29","doi-asserted-by":"publisher","first-page":"D92","DOI":"10.1093\/nar\/gkt1248","volume":"42","author":"JH Li","year":"2014","unstructured":"Li, J. H., Liu, S., Zhou, H., Qu, L. H. & Yang, J. H. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 42, D92\u2013D97 (2014).","journal-title":"Nucleic Acids Res."},{"key":"3591_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molcel.2008.12.013","volume":"33","author":"MT Bedford","year":"2009","unstructured":"Bedford, M. T. & Clarke, S. G. Protein arginine methylation in mammals: who, what, and why. Mol. Cell 33, 1\u201313 (2009).","journal-title":"Mol. Cell"},{"key":"3591_CR31","doi-asserted-by":"publisher","first-page":"7844","DOI":"10.1093\/nar\/gky634","volume":"46","author":"S Battaglia-Hsu","year":"2018","unstructured":"Battaglia-Hsu, S. et al. Inherited disorders of cobalamin metabolism disrupt nucleocytoplasmic transport of mRNA through impaired methylation\/phosphorylation of ELAVL1\/HuR. Nucleic Acids Res. 46, 7844\u20137857 (2018).","journal-title":"Nucleic Acids Res."},{"key":"3591_CR32","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1357-2725(99)00139-9","volume":"32","author":"SC Lu","year":"2000","unstructured":"Lu, S. C. S-Adenosylmethionine. Int. J. Biochem. Cell Biol. 32, 391\u2013395 (2000).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"3591_CR33","doi-asserted-by":"publisher","first-page":"4134053","DOI":"10.1155\/2016\/4134053","volume":"2016","author":"T Guo","year":"2016","unstructured":"Guo, T., He, Y., Ma, W., Liu, Z. & Liu, Q. Feasibility and efficacy of S-adenosyl-L-methionine in patients with HBV-related HCC with different BCLC stages. Gastroenterol. Res. Pract. 2016, 4134053 (2016).","journal-title":"Gastroenterol. Res. Pract."},{"key":"3591_CR34","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1097\/MEG.0000000000001141","volume":"30","author":"SI Mora","year":"2018","unstructured":"Mora, S. I., Garc\u00eda-Rom\u00e1n, J., G\u00f3mez-\u00d1a\u00f1ez, I. & Garc\u00eda-Rom\u00e1n, R. Chronic liver diseases and the potential use of S-adenosyl-L-methionine as a hepatoprotector. Eur. J. Gastroenterol. Hepatol. 30, 893\u2013900 (2018).","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"3591_CR35","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1007\/s00726-014-1913-x","volume":"47","author":"R Deminice","year":"2015","unstructured":"Deminice, R. et al. Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism. Amino Acids 47, 839\u2013846 (2015).","journal-title":"Amino Acids"},{"key":"3591_CR36","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.3945\/jn.111.144857","volume":"141","author":"R Deminice","year":"2011","unstructured":"Deminice, R. et al. Creatine supplementation prevents the accumulation of fat in the livers of rats fed a high-fat diet. J. Nutr. 141, 1799\u20131804 (2011).","journal-title":"J. Nutr."},{"key":"3591_CR37","doi-asserted-by":"publisher","first-page":"389","DOI":"10.2165\/00003495-198938030-00004","volume":"38","author":"HA Friedel","year":"1989","unstructured":"Friedel, H. A., Goa, K. L. & Benfield, P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 38, 389\u2013416 (1989).","journal-title":"Drugs"},{"key":"3591_CR38","doi-asserted-by":"publisher","first-page":"1773-","DOI":"10.1097\/01.ALC.0000108654.77178.03","volume":"28","author":"TD Lee","year":"2004","unstructured":"Lee, T. D. et al. Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis. Alcohol Clin. Exp. Res. 28, 1773-\u201311781 (2004).","journal-title":"Alcohol Clin. Exp. Res."},{"key":"3591_CR39","doi-asserted-by":"publisher","first-page":"407","DOI":"10.3109\/00365528909093067","volume":"24","author":"G Vendemiale","year":"1989","unstructured":"Vendemiale, G. et al. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scand. J. Gastroenterol. 24, 407\u2013415 (1989).","journal-title":"Scand. J. Gastroenterol."},{"key":"3591_CR40","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/j.jhep.2012.04.041","volume":"57","author":"QM Anstee","year":"2012","unstructured":"Anstee, Q. M. & Day, C. P. S-adenosylmethionine (SAMe) therapy in liver disease: a review of current evidence and clinical utility. J. Hepatol. 57, 1097\u20131109 (2012).","journal-title":"J. Hepatol."},{"key":"3591_CR41","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1053\/j.gastro.2013.07.047","volume":"145","author":"SK Murphy","year":"2013","unstructured":"Murphy, S. K. et al. Relationship between methylome and transcriptome in patients with nonalcoholic fatty liver disease. Gastroenterology 145, 1076\u20131087 (2013).","journal-title":"Gastroenterology"},{"key":"3591_CR42","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/hep.26661","volume":"59","author":"CA Moylan","year":"2014","unstructured":"Moylan, C. A. et al. Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease. Hepatology 59, 471\u2013482 (2014).","journal-title":"Hepatology"},{"key":"3591_CR43","first-page":"G125","volume":"275","author":"RK Chawla","year":"1998","unstructured":"Chawla, R. K. et al. S-adenosylmethionine deficiency and TNF-alpha in lipopolysaccharide-induced hepatic injury. Am. J. Physiol. 275, G125\u2013G129 (1998).","journal-title":"Am. J. Physiol."},{"key":"3591_CR44","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1161\/HYPERTENSIONAHA.111.00919","volume":"62","author":"JD Feltenberger","year":"2013","unstructured":"Feltenberger, J. D. et al. Oral formulation of angiotensin-(1-7) improves lipid metabolism and prevents high-fat diet-induced hepatic steatosis and inflammation in mice. Hypertension 62, 324\u2013330 (2013).","journal-title":"Hypertension"},{"key":"3591_CR45","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1161\/01.ATV.0000140059.04717.f3","volume":"24","author":"M Mario","year":"2004","unstructured":"Mario, M., David, F., David, S. & David, S. Angiotensin II induced insulin resistance and protein tyrosine phosphatases. Arterioscler. Thromb. Vasc. Biol. 24, 2009\u20132013 (2004).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"3591_CR46","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1161\/01.CIR.0000141736.76561.78","volume":"110","author":"P Abhiram","year":"2004","unstructured":"Abhiram, P. & Arshed, A. Q. Renin-angiotensin system and angiotensin receptor blockers in the metabolic syndrome. Circulation 110, 1507\u20131512 (2004).","journal-title":"Circulation"},{"key":"3591_CR47","doi-asserted-by":"publisher","first-page":"35137","DOI":"10.1074\/jbc.M601320200","volume":"281","author":"Y Wei","year":"2006","unstructured":"Wei, Y. et al. Angiotensin II-induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells. J. Biol. Chem. 281, 35137\u201335146 (2006).","journal-title":"J. Biol. Chem."},{"key":"3591_CR48","doi-asserted-by":"publisher","first-page":"H1219","DOI":"10.1152\/ajpheart.00796.2011","volume":"302","author":"P Kelly","year":"2012","unstructured":"Kelly, P., Robin, S., Frederique, Y. & Lisa, A. C. The reninangiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am. J. Physiol. Heart Circ. Physiol. 302, H1219\u2013H1230 (2012).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"3591_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/wrna.1372","volume":"8","author":"I Grammatikakis","year":"2017","unstructured":"Grammatikakis, I., Abdelmohsen, K. & Gorospe, M. Posttranslational control of HuR function. Wiley Interdiscip. Rev. RNA 8, 1 (2017).","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"3591_CR50","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/nar\/gkp1114","volume":"38","author":"J Yi","year":"2010","unstructured":"Yi, J. et al. Reduced nuclear export of HuR mRNA by HuR is linked to the loss of HuR in replicative senescence. Nucleic Acids Res. 38, 1547\u20131558 (2010).","journal-title":"Nucleic Acids Res."},{"key":"3591_CR51","doi-asserted-by":"publisher","first-page":"3145","DOI":"10.1242\/jcs.111.21.3145","volume":"111","author":"U Atasoy","year":"1998","unstructured":"Atasoy, U., Watson, J., Patel, D. & Keene, J. D. ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is upregulated during serum stimulation and T cell activation. J. Cell Sci. 111, 3145\u20133156 (1998).","journal-title":"J. Cell Sci."},{"key":"3591_CR52","doi-asserted-by":"publisher","first-page":"44623","DOI":"10.1074\/jbc.M206187200","volume":"277","author":"H Li","year":"2002","unstructured":"Li, H. et al. Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. J. Biol. Chem. 277, 44623\u201344630 (2002).","journal-title":"J. Biol. Chem."},{"key":"3591_CR53","doi-asserted-by":"publisher","first-page":"26040","DOI":"10.1074\/jbc.M910460199","volume":"275","author":"F Rodriguez-Pascual","year":"2000","unstructured":"Rodriguez-Pascual, F. et al. Complex contribution of the 3\u2019-untranslated region to the expressional regulation of the human inducible nitric-oxide synthase gene. Involvement of the RNA-binding protein HuR. J. Biol. Chem. 275, 26040\u201326049 (2000).","journal-title":"J. Biol. Chem."},{"key":"3591_CR54","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1101\/gad.1645808","volume":"22","author":"HH Kim","year":"2008","unstructured":"Kim, H. H. et al. Nuclear HuR accumulation through phosphorylation by Cdk1. Genes Dev. 22, 1804\u20131815 (2008).","journal-title":"Genes Dev."},{"key":"3591_CR55","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.tibs.2005.10.002","volume":"30","author":"FO Fackelmayer","year":"2005","unstructured":"Fackelmayer, F. O. Protein arginine methyltransferases: guardians of the Arg? Trends Biochem. Sci. 30, 666\u2013671 (2005).","journal-title":"Trends Biochem. Sci."},{"key":"3591_CR56","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1515\/BC.2008.022","volume":"389","author":"K Abdelmohsen","year":"2008","unstructured":"Abdelmohsen, K., Kuwano, Y., Kim, H. H. & Gorospe, M. Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence. Biol. Chem. 389, 243\u2013255 (2008).","journal-title":"Biol. Chem."},{"key":"3591_CR57","doi-asserted-by":"publisher","first-page":"2608","DOI":"10.1128\/MCB.01530-07","volume":"28","author":"A Doller","year":"2008","unstructured":"Doller, A. et al. Posttranslational modification of the AU-rich element binding protein HuR by protein kinase Cdelta elicits angiotensin II-induced stabilization and nuclear export of cyclooxygenase 2 mRNA. Mol. Cell Biol. 28, 2608\u20132625 (2008).","journal-title":"Mol. Cell Biol."},{"key":"3591_CR58","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1126\/science.1064693","volume":"294","author":"IE Gallouzi","year":"2001","unstructured":"Gallouzi, I. E. & Steitz, J. A. Delineation of mRNA export pathways by the use of cell-permeable peptides. Science 294, 1895\u20131901 (2001).","journal-title":"Science"},{"key":"3591_CR59","doi-asserted-by":"publisher","first-page":"10912","DOI":"10.1074\/jbc.M510306200","volume":"281","author":"AT Prechtel","year":"2006","unstructured":"Prechtel, A. T. et al. Expression of CD83 is regulated by HuR via a novel cis-active coding region RNA element. J. Biol. Chem. 281, 10912\u201310925 (2006).","journal-title":"J. Biol. Chem."}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03591-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03591-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03591-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T01:04:45Z","timestamp":1675040685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03591-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":59,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["3591"],"URL":"https:\/\/doi.org\/10.1038\/s41419-021-03591-1","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"18 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The relevant protocols were confirmed through the Human Subjects Committee of Zhongnan Hospital of Wuhan University and Second Affiliated Hospital of Chongqing Medical University conforming to the Declaration of Helsinki.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"306"}}