Cav 1.2 and Cav 2.2 expression is regulated by different endogenous ghrelin levels in pancreatic acinar cells during acute pancreatitis

Zhou,Jie; Qin,Mengbin; Wang,Huilin; He,Jiaping; Fu,Hongzong; Shi,Huirong; Liang,Zhihai; Tang,Guodu

doi:10.3892/ijmm.2018.3490

Cav 1.2 and Cav 2.2 expression is regulated by different endogenous ghrelin levels in pancreatic acinar cells during acute pancreatitis

Authors:
- Jie Zhou
- Mengbin Qin
- Huilin Wang
- Jiaping He
- Hongzong Fu
- Huirong Shi
- Zhihai Liang
- Guodu Tang
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Affiliations: Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: February 13, 2018 https://doi.org/10.3892/ijmm.2018.3490
Pages: 2909-2916

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Abstract

Ghrelin influences pancreatic endocrine and exocrine functions, regulates intracellular calcium [Ca2+]i levels, and has an anti-inflammatory role in acute pancreatitis. This study investigated the role of endogenous ghrelin in the expression of Cav 1.2 (L-type of Ca2+ channel) and Cav 2.2 (N-type of Ca2+ channel) in acute pancreatitis. For this purpose, acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) rat models were established. Cav 1.2 and Cav 2.2 expression was assessed by immunohistochemistry in the pancreatic tissues of rats; ghrelin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serum levels were detected using ELISA. Next, in AR42J cells with either knock-out or overexpression of ghrelin, Cav 1.2 and Cav 2.2 expression was examined using western blot analysis, and intracellular calcium [Ca2+]i was detected with confocal microscopy. In this study, the ghrelin serum level was highest in the ANP group and was higher in the AEP group than the normal group. Expression of Cav 1.2 and Cav 2.2 in the ANP and AEP groups was higher than in the respective control groups. The serum IL-1β and TNF-α levels were significantly higher in the ANP group compared to the other groups. Cav 1.2 and Cav 2.2 expression and [Ca2+]i decreased in ghrelin knockdown AR42J cells but increased in ghrelin overexpressing cells. In conclusion, Cav 1.2 and Cav 2.2 expression increased in ANP. The [Ca2+]i level, which is mediated by Cav 1.2 and Cav 2.2 expression, is directly regulated by ghrelin in pancreatic acinar cells, and serum ghrelin levels may be involved in the severity of acute pancreatitis.

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