The gene expression of adrenomedullin, calcitonin-receptor-like receptor and receptor activity modifying proteins (RAMPs) in CCl4-induced rat liver cirrhosis.
This study was undertaken to determine AM expression in carbon tetrachloride (CCl4)-induced liver cirrhosis developed with peritoneal ascites. Sprague-Dawley rats received subcutaneous injections of CCl4 twice weekly in olive oil (1:1, 0.3 ml per kg body weight) for 6 or 12 weeks until ascites developed, or saline in olive oil as control. At 6 weeks, fibrosis developed and at 12 weeks cirrhosis developed with ascites formation. At both 6 and 12 weeks, increases in plasma renin and AM were evident, as was the gene expression of AM. At 12 weeks after CCl4 injection, the gene expression of calcitonin-like-receptor (CRLR) and receptor activity modifying proteins (RAMP1, RAMP2 and RAMP3) were all elevated when compared to the control. The results suggest that liver cirrhosis increases mRNA expressions of AM, CRLR and RAMP1, RAMP2 and RAMP3 and that the increase in AM gene expression precedes the development of cirrhosis. The increase in AM synthesis as reflected by an increase in AM gene expression, together with a lack of increase in AM peptide at both 6 and 12 weeks may suggest an elevation of AM release. Given the potent vasodilatory action of AM, the increase in the synthesis and release of AM in the cirrhotic liver may also contribute to peripheral vasodilatation in liver cirrhosis.
Hwang
Isabel Shui Shan
IS
Center for the Study of Liver Disease, The University of Hong Kong, Pokfulam, Hong Kong, China.
Tang
Fai
F
Leung
Pauline P
PP
Li
Yuk Yin
YY
Fan
Sheung Tat
ST
Luk
John Moon Ching
JM
D053607:Adrenomedullin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D058286:Calcitonin Receptor-Like Protein; D002251:Carbon Tetrachloride / Q000633:toxicity*; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000097:blood
D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009566:Nitrates; D009573:Nitrites; D020033:Protein Isoforms; C545508:Ramp1 protein, rat; C545509:Ramp2 protein, rat; C545510:Ramp3 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D053607:Adrenomedullin; D002251:Carbon Tetrachloride; D012083:Renin