Upregulation of pancreatic derived factor (FAM3B) expression in pancreatic β-cells by MCP-1 (CCL2)

Upregulation of pancreatic derived factor (FAM3B) expression in pancreatic β-cells by MCP-1 (CCL2)
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DOI:
10.1016/j.mce.2011.05.039
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发表时间:
2011-08-22
影响因子:
4.1
通讯作者:
Le, Yingying
Le, Yingying
中科院分区:
医学2区
文献类型:
--
作者:
Hou, Xinwei;Wang, Oumei;Le, Yingying

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Pancreatic derived factor (PANDER, FAM3B) is a peptide mainly synthesized and secreted by pancreatic beta-cells. PANDER is proposed to be involved in regulation of beta-cell function under physiological conditions and impairment of beta-cell function under pathological conditions. MCP-1 (CCL2) is expressed by normal pancreatic islets and has been implicated in inflammation related pancreatic disorders. We examined the effect of MCP-1 on PANDER expression by using murine pancreatic beta-cell line MIN6 and pancreatic islets. We found that MCP-1 induced PANDER mRNA transcription and protein synthesis in MIN6 cells and islets. By using calcium chelator (EGTA); inhibitors for PKC (Go6976), MEK1/2 (PD98059) or c-Jun-N-terminal kinase (JNK) (SP600125); c-Jun dominant-negative construct; PANDER promoter luciferase constructs; and islets isolated from Fos knockout mice; we demonstrated that MCP-1 induced PANDER gene expression in beta-cells through Ca2+-ERK1/2-AP-1 and PKC-JNK-AP-1 signaling pathways. Our findings suggest a new link between the endocrine and immune systems and provide useful information for further investigating the physiological functions of PANDER and its involvement in inflammation-related pancreatic disorders. (C) 2011 Elsevier Ireland Ltd. All rights reserved.