title: Upregulation of pancreatic derived factor (FAM3B) expression in pancreatic β-cells by MCP-1 (CCL2).
abstract: Pancreatic derived factor (PANDER, FAM3B) is a peptide mainly synthesized and secreted by pancreatic β-cells. PANDER is proposed to be involved in regulation of β-cell function under physiological conditions and impairment of β-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 β-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 β-cells through Ca(2+)-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.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Hou
authors.forename: Oumei
authors.initials: O
authors.lastname: Wang
authors.forename: Zongmeng
authors.initials: Z
authors.lastname: Li
authors.forename: Haiwei
authors.initials: H
authors.lastname: Mou
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Deng
authors.forename: Lihua
authors.initials: L
authors.lastname: Qian
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Le
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; C504749:PANDER protein, mouse; D012333:RNA, Messenger; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D002118:Calcium