MCP-1 Upregulates Amylin Expression in Murine Pancreatic beta Cells through ERK/JNK-AP1 and NF-kappa B Related Signaling Pathways Independent of CCR2

	MCP-1 Upregulates Amylin Expression in Murine Pancreatic beta Cells through ERK/JNK-AP1 and NF-kappa B Related Signaling Pathways Independent of CCR2
	Cai, K; Qi, DF; Hou, XW; Wang, OM; Chen, J; Deng, B; Qian, LH; Liu, XL; Le, YY
刊名	PLOS ONE
	2011
卷号	6 期号:5 页码:e19559-e19559
通讯作者	Cai, K (reprint author), Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China.,yyle@sibs.ac.cn
英文摘要	Background: Amylin is the most abundant component of islet amyloid implicated in the development of type 2 diabetes. Plasma amylin levels are elevated in individuals with obesity and insulin resistance. Monocyte chemoattractant protein-1 (MCP-1, CCL2) is involved in insulin resistance of obesity and type 2 diabetes. We investigated the effect of MCP-1 on amylin expression and the underlying mechanisms with murine pancreatic beta-cell line MIN6 and pancreatic islets. Methodology/Principal Findings: We found that MCP-1 induced amylin expression at transcriptional level and increased proamylin and intermediate forms of amylin at protein level in MIN6 cells and islets. However, MCP-1 had no effect on the expressions of proinsulin 1 and 2, as well as prohormone convertase (PC) 1/3 and PC2, suggesting that MCP-1 specifically induces amylin expression in beta-cells. Mechanistic studies showed that although there is no detectable CCR2 mRNA in MIN6 cells and islets, pretreatment of MIN6 cells with pertussis toxin inhibited MCP-1 induced amylin expression, suggesting that alternative Gi-coupled receptor(s) mediates the inductive effect of MCP-1. MCP-1 rapidly induced ERK1/2 and JNK phosphorylation. Inhibitors for MEK1/2 (PD98059), JNK (SP600125) or AP1 (curcumin) significantly inhibited MCP-1-induced amylin mRNA expression. MCP-1 failed to induce amylin expression in pancreatic islets isolated from Fos knockout mice. EMSA showed that JNK and ERK1/2 were involved in MCP-1-induced AP1 activation. These results suggest that MCP-1 induces murine amylin expression through AP1 activation mediated by ERK1/2 or JNK. Further studies showed that treatment of MIN6 cells with NF-kappa B inhibitor or overexpression of I kappa B alpha dominant-negative construct in MIN6 cells significantly inhibited MCP-1-induced amylin expression, suggesting that NF-kappa B related signaling also participates in MCP-1-induced murine amylin expression. Conclusions/Significance: MCP-1 induces amylin expression through ERK1/2/JNK-AP1 and NF-kappa B related signaling pathways independent of CCR2. Amylin upregulation by MCP-1 may contribute to elevation of plasma amylin in obesity and insulin resistance.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	ISLET AMYLOID POLYPEPTIDE ; MONOCYTE CHEMOATTRACTANT PROTEIN-1 ; DEPENDENT DIABETES-MELLITUS ; AORTIC SMOOTH-MUSCLE ; INSULIN-RESISTANCE ; ADIPOSE-TISSUE ; SKELETAL-MUSCLE ; OBESE SUBJECTS ; WEIGHT-LOSS ; IN-VIVO
收录类别	SCI
语种	英语
WOS记录号	WOS:000290483600016
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/792]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Cai, K,Qi, DF,Hou, XW,et al. MCP-1 Upregulates Amylin Expression in Murine Pancreatic beta Cells through ERK/JNK-AP1 and NF-kappa B Related Signaling Pathways Independent of CCR2[J]. PLOS ONE,2011,6(5):e19559-e19559.
APA	Cai, K.,Qi, DF.,Hou, XW.,Wang, OM.,Chen, J.,...&Le, YY.(2011).MCP-1 Upregulates Amylin Expression in Murine Pancreatic beta Cells through ERK/JNK-AP1 and NF-kappa B Related Signaling Pathways Independent of CCR2.PLOS ONE,6(5),e19559-e19559.
MLA	Cai, K,et al."MCP-1 Upregulates Amylin Expression in Murine Pancreatic beta Cells through ERK/JNK-AP1 and NF-kappa B Related Signaling Pathways Independent of CCR2".PLOS ONE 6.5(2011):e19559-e19559.