{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:52:43Z","timestamp":1790452363767,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2010,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>There are no effective antifibrotic therapies for patients with liver diseases. We performed an experimental and translational study to investigate whether ghrelin, an orexigenic hormone with pleiotropic properties, modulates liver fibrogenesis. Recombinant ghrelin was administered to rats with chronic (bile duct ligation) and acute (carbon tetrachloride) liver injury. Hepatic gene expression was analyzed by way of microarray analysis and quantitative polymerase chain reaction. The hepatic response to chronic injury was also evaluated in wild-type and ghrelin-deficient mice. Primary human hepatic stellate cells were used to study the effects of ghrelin<\/jats:bold>\n                                 <jats:bold>\n                                    in vitro\n                                 <\/jats:bold>\n                                 <jats:bold>. Ghrelin hepatic gene expression and serum levels were assessed in patients with chronic liver diseases. Ghrelin gene polymorphisms were analyzed in patients with chronic hepatitis C. Recombinant ghrelin treatment reduced the fibrogenic response, decreased liver injury and myofibroblast accumulation, and attenuated the altered gene expression profile in bile duct\u2013ligated rats. Moreover, ghrelin reduced the fibrogenic properties of hepatic stellate cells. Ghrelin also protected rats from acute liver injury and reduced the extent of oxidative stress and inflammation. Ghrelin-deficient mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis, and ghrelin gene hepatic expression correlated with expression of fibrogenic genes. In patients with chronic hepatitis C, polymorphisms of the ghrelin gene (\u2212994CT and \u2212604GA) influenced the progression of liver fibrosis.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>Ghrelin exerts antifibrotic effects in the liver and may represent a novel antifibrotic therapy. (Hepatology 2010;51:974\u2013985.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.23421","type":"journal-article","created":{"date-parts":[[2009,11,9]],"date-time":"2009-11-09T14:32:57Z","timestamp":1257777177000},"page":"974-985","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":132,"title":["Ghrelin Attenuates Hepatocellular Injury and Liver Fibrogenesis in Rodents and Influences Fibrosis Progression in Humans"],"prefix":"10.1097","volume":"51","author":[{"given":"Montserrat","family":"Moreno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier F.","family":"Chaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Sancho-Bru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Ramalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandra N.","family":"Ramalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Mansego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Ivorra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Conde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mill\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Mar\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Colmenero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Lozano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Jares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Forns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Arroyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Caballer\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pere","family":"Gin\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Bataller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-28-20241201","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis.","volume":"115","author":"Bataller","year":"2005","journal-title":"J Clin Invest"},{"key":"R2-28-20241201","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1152\/physrev.00012.2004","article-title":"Ghrelin: structure and function.","volume":"85","author":"Kojima","year":"2005","journal-title":"Physiol Rev"},{"key":"R3-28-20241201","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1210\/er.2002-0029","article-title":"Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin.","volume":"25","author":"van der Lely","year":"2004","journal-title":"Endocr Rev"},{"key":"R4-28-20241201","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1210\/jcem.87.6.8739","article-title":"The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHSR, in humans.","volume":"87","author":"Gnanapavan","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"R5-28-20241201","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1083\/jcb.200207165","article-title":"Ghrelin and desacyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK12 and PI 3kinaseAKT.","volume":"159","author":"Baldanzi","year":"2002","journal-title":"J Cell Biol"},{"key":"R6-28-20241201","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1053\/j.gastro.2006.01.041","article-title":"Therapeutic action of ghrelin in a mouse model of colitis.","volume":"130","author":"GonzalezRey","year":"2006","journal-title":"Gastroenterology"},{"key":"R7-28-20241201","doi-asserted-by":"crossref","first-page":"RC19","DOI":"10.1007\/BF03347367","article-title":"Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HITT15 pancreatic betacells.","volume":"29","author":"Granata","year":"2006","journal-title":"J Endocrinol Invest"},{"key":"R8-28-20241201","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/j.1745-7254.2006.00319.x","article-title":"Cardioprotective effects of ghrelin and desoctanoyl ghrelin on myocardial injury induced by isoproterenol in rats.","volume":"27","author":"Li","year":"2006","journal-title":"Acta Pharmacol Sin"},{"key":"R9-28-20241201","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1210\/jc.2003-031768","article-title":"Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebocontrolled trial.","volume":"89","author":"Neary","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"R10-28-20241201","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1681\/ASN.2005010039","article-title":"Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance peritoneal dialysis: a randomized, placebocontrolled trial.","volume":"16","author":"Wynne","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"R11-28-20241201","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.peptides.2005.12.008","article-title":"Ghrelin gastrokinetic action in patients with neurogenic gastroparesis.","volume":"27","author":"Binn","year":"2006","journal-title":"Peptides"},{"key":"R12-28-20241201","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.1161\/01.CIR.0000149746.62908.BB","article-title":"Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure.","volume":"110","author":"Nagaya","year":"2004","journal-title":"Circulation"},{"key":"R13-28-20241201","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1378\/chest.128.3.1187","article-title":"Treatment of cachexia with ghrelin in patients with COPD.","volume":"128","author":"Nagaya","year":"2005","journal-title":"Chest"},{"key":"R14-28-20241201","first-page":"1499","article-title":"Effect of losartan, an angiotensin II antagonist, on secondary biliary cirrhosis.","volume":"49","author":"Ramalho","year":"2002","journal-title":"Hepatogastroenterology"},{"key":"R15-28-20241201","doi-asserted-by":"crossref","first-page":"8227","DOI":"10.1073\/pnas.0402763101","article-title":"Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference.","volume":"101","author":"Wortley","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R16-28-20241201","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/bjs.6050","article-title":"Characterization of timerelated changes after experimental bile duct ligation.","volume":"95","author":"Georgiev","year":"2008","journal-title":"Br J Surg"},{"key":"R17-28-20241201","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1053\/j.gastro.2006.12.036","article-title":"Hepatic expression of candidate genes in patients with alcoholic hepatitis: correlation with disease severity.","volume":"132","author":"Colmenero","year":"2007","journal-title":"Gastroenterology"},{"key":"R18-28-20241201","first-page":"BR141","article-title":"Ghrelin attenuates lipopolysaccharideinduced acute lung injury through NO pathway.","volume":"14","author":"Chen","year":"2008","journal-title":"Med Sci Monit"},{"key":"R19-28-20241201","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1097\/00005344-200402000-00001","article-title":"Protective effects of ghrelin on ischemiareperfusion injury in the isolated rat heart.","volume":"43","author":"Chang","year":"2004","journal-title":"J Cardiovasc Pharmacol"},{"key":"R20-28-20241201","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.regpep.2007.08.014","article-title":"Ghrelin alleviates biliary obstructioninduced chronic hepatic injury in rats.","volume":"146","author":"Iseri","year":"2008","journal-title":"Regul Pept"},{"key":"R21-28-20241201","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1210\/en.2006-0266","article-title":"Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic betacells and human islets: involvement of 3,5cyclic adenosine monophosphateprotein kinase A, extracellular signalregulated kinase 12, and phosphatidyl inositol 3kinaseAkt signaling.","volume":"148","author":"Granata","year":"2007","journal-title":"Endocrinology"},{"key":"R22-28-20241201","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0168-8278(02)00438-5","article-title":"Ghrelin in chronic liver disease.","volume":"38","author":"Tacke","year":"2003","journal-title":"J Hepatol"},{"key":"R23-28-20241201","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1530\/eje.0.1440687","article-title":"Gender and gonadal influences on ghrelin mRNA levels in rat stomach.","volume":"144","author":"Gualillo","year":"2001","journal-title":"Eur J Endocrinol"},{"key":"R24-28-20241201","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.clnu.2008.12.002","article-title":"Influence of age, gender, and glucose tolerance on fasting and fed acylated ghrelin in Prader Willi syndrome.","volume":"28","author":"Prodam","year":"2009","journal-title":"Clin Nutr"},{"key":"R25-28-20241201","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/sj.ijo.0803296","article-title":"Preproghrelin Leu72Met variant contributes to overweight in middleaged men of a Japanese large cohort.","volume":"30","author":"Kuzuya","year":"2006","journal-title":"Int J Obes (Lond)"},{"key":"R26-28-20241201","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/oby.2002.106","article-title":"Role of ghrelin polymorphisms in obesity based on three different studies.","volume":"10","author":"Ukkola","year":"2002","journal-title":"Obes Res"},{"key":"R27-28-20241201","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1872-034X.2007.00032.x","article-title":"Protection of estrogens against the progression of chronic liver disease.","volume":"37","author":"Shimizu","year":"2007","journal-title":"Hepatol Res"},{"key":"R28-28-20241201","first-page":"325","article-title":"Ghrelina new gastroprotective factor in gastric mucosa.","volume":"55","author":"Konturek","year":"2004","journal-title":"J Physiol Pharmacol"},{"key":"R29-28-20241201","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1210\/en.2006-0991","article-title":"Ghrelin inhibits apoptosis in hypothalamic neuronal cells during oxygenglucose deprivation.","volume":"148","author":"Chung","year":"2007","journal-title":"Endocrinology"},{"key":"R30-28-20241201","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1111\/j.1440-1746.2006.04696.x","article-title":"In vivo and in vitro antioxidant activity of ghrelin: Attenuation of gastric ischemic injury in the rat.","volume":"22","author":"El","year":"2007","journal-title":"J Gastroenterol Hepatol"},{"key":"R31-28-20241201","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.peptides.2007.11.020","article-title":"Dose dependent effects of ghrelin on pentylenetetrazoleinduced oxidative stress in a rat seizure model.","volume":"29","author":"Obay","year":"2008","journal-title":"Peptides"},{"key":"R32-28-20241201","doi-asserted-by":"crossref","first-page":"6320","DOI":"10.1073\/pnas.0800708105","article-title":"Ghrelin octanoylation mediated by an orphan lipid transferase.","volume":"105","author":"Gutierrez","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R33-28-20241201","doi-asserted-by":"crossref","first-page":"5202","DOI":"10.1021\/jm070071+","article-title":"Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.","volume":"50","author":"Rudolph","year":"2007","journal-title":"J Med Chem"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.23421","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201003000-00028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T13:33:48Z","timestamp":1733060028000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201003000-00028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.23421","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2010,3]]}}}