Cyclooxygenase-2 up-regulates hepatic somatostatin receptor 2 expression

• Published in: Scientific reports Vol. 8; no. 1; pp. 11033 - 11
• Main Authors: Lu, Yao-Yao, Gao, Jin-Hang, Zhao, Chong, Wen, Shi-Lei, Tang, Cheng-Wei, Wang, Yu-Fang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.07.2018; Nature Publishing Group
• Subjects: 13/1; 13/44; 13/51; 13/95; 14/63; 38; 38/23; 38/39; 38/44; 38/77; 59; 692/4020/4021/1607/1604; 692/4020/4021/288/2032; 96/47; Celecoxib; Cirrhosis; Cyclic AMP response element-binding protein; Cyclooxygenase-2; Deoxyribonucleic acid; DNA; DNA methylation; Humanities and Social Sciences; Kinases; Liver; Liver cirrhosis; multidisciplinary; Plasmids; Protein kinase C; Receptor mechanisms; Science; Science (multidisciplinary); Signal transduction; Somatostatin; Somatostatin receptors; Thioacetamide; Transfection
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-29349-y

Somatostatin and its analogues, which function by binding to somatostatin receptors (SSTRs) 1–5, play a protective role in liver cirrhosis. Hepatic SSTR-2 expression is up-regulated in subjects with liver cirrhosis. However, little is known about the mechanisms underlying this process. In the present study, we observed the up-regulation of hepatic SSTR-2 expression in thioacetamide (TAA)-induced cirrhotic rats and further showed that cyclooxygenase-2 (COX-2) might play a role in this process via the protein kinase C (PKC)–cAMP response element binding protein (CREB) signaling pathway. In vivo , the up-regulated SSTR-2 in liver cirrhosis was inhibited by the addition of a selective COX-2 inhibitor, such as celecoxib. In vitro , the up-regulation of COX-2 by either transfection with COX-2 plasmids or treatment with TAA increased levels of SSTR-2 and phosphorylated CREB (p-CREB) in the human hepatocyte cell line L02. Furthermore, the increase in SSTR-2 expression was inhibited by the addition of celecoxib and a PKC inhibitor. Moreover, for comparable DNA methylation levels in the region upstream of the hepatic SSTR-2 gene in normal and cirrhotic livers, DNA methylation may not contribute to the up-regulation of SSTR-2 expression in cirrhotic livers. In conclusion, the up-regulation of hepatic SSTR-2 might be induced by COX-2 via the PKC-CREB signaling pathway but is probably not induced by DNA methylation.