Abstract
Purpose
Apelin, the endogenous ligand of the angiotensin-like-receptor 1 (APJ), is thought to play an important role in liver disease. This study investigated the apelin expression in different stages of biliary atresia (BA) and investigated whether it is associated with the progression of disease.
Methods
Liver tissues were obtained from patients at Kasai’s procedure (KP), the follow-up stage after KP (Post-KP) and at liver transplantation (LT). Immunohistochemistry for apelin and its receptor APJ and real-time quantitative reverse transcriptase polymerase chain reaction for apelin mRNA expression were conducted.
Results
The immunohistochemical study revealed that apelin was mainly localized in the perivenular areas of control liver tissue, and slightly detected in the hepatic stellate cells (HSC) and hepatocytes, whereas intense apelin immunoreactivity was detected in perivenular areas, HSC and hepatocytes of LT liver tissue. The apelin mRNA expression level was significantly higher in the LT group than in the KP and Post-KP group. Significant linear correlations were observed between the apelin mRNA level and liver fibrosis, serum total bilirubin and the grade of esophageal varices.
Conclusions
The hepatic apelin–APJ system is markedly activated in the progression of BA, especially in end-stage cirrhosis. The apelin expression level accurately reflects the severity of hepatic fibrosis and esophageal varices and therefore could be used as a prognostic factor in BA patients.
Similar content being viewed by others
References
Tatemoto K, Hosoya M, Habata Y et al (1998) Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 25:471–476
O’Dowd BF, Heiber M, Chan A et al (1993) A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene 136(1–2):355–360
Ishida J, Hashimoto T, Hashimoto Y et al (2004) Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. J Biol Chem 279:26274–26279
Szokodi I, Tavi P, Foldes G et al (2002) Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cadiac contractility. Circ Res 91:434–440
Boucher J, Masri B, Daviaud D et al (2005) Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology 146:1764–1771
Wang G, Anini Y, Wei W et al (2004) Apelin, a new enteric peptide: localization in the gastrointestinal tract, ontogeny, and stimulation of gastric cell proliferation and of cholecystokinin secretion. Endocrinology 145:1342–1348
De Mota N, Reaux-Le Goazigo A, El Messari S et al (2004) Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc Natl Acad Sci 101:10464–10469
Hiroaki Y, Masaya O, Kazunori Y et al (2011) Overexpression of apelin receptor (APJ/AGTRL1) on hepative stellate cells and sinusoidal angiogenesis in human cirrhotic liver. J Gastroenterol 46:222–231
Principe A, Melgar-Lesmes P, Ferna′ndez-Varo G et al (2008) The hepatic apelin system: a new therapeutic target for liver disease. Hepatology 48:1193–1201
Yokomori H, Oda M, Yoshimura K et al (2012) Enhanced expressions of apelin on proliferative hepatic arterial capillaries in human cirrhotic liver. Hepatol Res 42(5):508–514
Okazaki T, Kobayashi H, Yamataka A et al (1999) Long-term postsurgical outcome of biliary atresia. J Pediatr Surg 34:312–315
Tajiri T, Yoshida H, Obara K et al (2010) General rules for recording endoscopic findings of esophagogastric varices (2nd edn). Dig Endosc 22:1–9
Ichida F, Tsuji T, Omata M et al (1996) New Inuyama classification for histological assessment of chronic hepatitis. Hepatol Commun 6:112–119
Lee DK, Cheng R, Nguyen T et al (2000) Characterization of apelin, the ligand for the APJ receptor. J Neurochem 74:34–41
Hosoya M, Kawamata Y, Fukusumi S et al (2000) Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem 275:21061–21067
Hiroaki Y, Masaya O, Kazunori Y et al (2012) Enhanced expression of apelin on proliferative hepatic arterial capillaries in human cirrhotic liver. Hepatol Res 42:508–514
Kasai M (1974) Treatment of biliary atresia with special reference to hepatic portoenterostomy and its modifications. Prog Pediatr Surg 6:5–52
Karrer FM, Price MR, Bensard DD, Sokol RJ, Narkewicz MR, Smith DJ et al (1996) Long-term results with the Kasai operation for biliary atresia. Arch Surg 131:493–496
Ohi R, Nio M, Chiba T, Endo N, Goto M, Ibrahim M (1990) Long-term follow-up after surgery for patients with biliary atresia. J Pediatr Surg 25:442–445
Tagge DU, Tagge EP, Drongowski RA, Oldham KT, Coran AGA (1991) Long term experience with biliary atresia. Ann Surg 214:590–598
Gautier M, Valayer J, Odièvre M et al (1984) Histological liver evaluation 5 years after surgery for extrahepatic biliary atresia: a study of 20 cases. J Pediatr Surg 19:263–268
Lykavieris P, Chardot C, Sokhn M et al (2005) Outcome in adulthood of biliary atresia: a study of 63 patients who survived for over 20 years with their native liver. Hepatology 41:366–371
Acknowledgments
This study was supported in part by the Japan–China Sasakawa Medical Fellowship.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, W., Oue, T., Ueno, T. et al. Apelin is a marker of the progression of liver fibrosis and portal hypertension in patients with biliary atresia. Pediatr Surg Int 29, 79–85 (2013). https://doi.org/10.1007/s00383-012-3210-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00383-012-3210-7