Macrophage migration inhibitory factor is overexpressed in pancreatic cancer tissues and impairs insulin secretion function of β-cell.
Macrophage migration inhibitory factor is overexpressed in pancreatic cancer tissues and impairs insulin secretion function of β-cell.
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巨噬细胞迁移抑制因子在胰腺癌组织中过度表达并损害β细胞的胰岛素分泌功能
DOI：
10.1186/1479-5876-12-92
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发表时间：
2014-04-07
影响因子：
7.4
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Tan L;Ye X;Zhou Y;Yu M;Fu Z;Chen R;Zhuang B;Zeng B;Ye H;Gao W;Lin Q;Li Z;Zhou Q;Chen R
了解胰腺癌相关糖尿病(PCDM)的发病机制可能有助于从新发糖尿病人群中获得早期诊断胰腺癌(PC)的生物标志物。在目前的研究中，我们试图确定巨噬细胞移动抑制因子(MIF)在PCDM发病机制中的作用。采用免疫组织化学和定量逆转录聚合酶链式反应检测石蜡包埋的人PC组织、慢性胰腺炎组织和正常胰腺组织中MIF的蛋白和mRNA水平。我们检测了PC患者和对照组的血清MIF水平。体外研究MIF过表达对小鼠胰岛和β细胞(HIT-T15)胰岛素分泌功能的影响。MIF在胰腺癌组织中的表达明显高于慢性胰腺炎和正常胰腺组织。胰岛细胞和HIT-T15细胞的胰岛素分泌功能均受到PC细胞的间接共培养和条件培养液的影响。稳定的MIF基因敲除可显著降低PC细胞的促糖尿病作用，而MIF基因敲除HPDE6细胞对胰岛和HIT-T15细胞的胰岛素分泌功能有较强的抑制作用。MIF通过抑制钙电流，降低L钙通道α1亚单位蛋白表达水平，增强p-Src活性，从而损害细胞功能。与其他组相比，初发糖尿病合并PC患者的平均血清MIF水平显著升高。MIF在胰腺癌患者中表达上调，并导致β细胞胰岛素分泌功能障碍。
Understanding the pathogenic mechanism of pancreatic cancer associated diabetes (PCDM) might help yield biomarkers for the early diagnosis of pancreatic cancer (PC) from population with new-onset diabetes. In the current study, we sought to determine the role of macrophage migration inhibitory factor (MIF) in PCDM pathogenesis. The protein and mRNA levels of MIF in paraffin-embedded human PC samples, chronic pancreatitis specimens, and normal pancreas were measured by immunohistochemistry and quantitative reverse-transcriptase polymerase chain reaction. We measured serum levels of MIF in PC patients and controls. The biologic impacts of MIF overexpression on insulin secretion function of mice islets and β cells (HIT-T15) were investigated in vitro. MIF expression was significantly increased in pancreatic cancer tissues compared with chronic pancreatitis or normal pancreas specimens. The insulin secretion function of both islets and HIT-T15 cells was impaired by indirect co-cultured with PC cells or treated with conditioned media from them. Stable MIF knock-down significantly decreased the diabetogenic effect of PC cells, while MIF knock-in HPDE6 cells demonstrated a strong inhibitory effect on insulin secretion function of islets and HIT-T15 cells. MIF impaired βcell function by depressing the Ca2+ currents, decreasing L-type Ca2+ channel α1 subunit protein expression level, and enhancing p-Src activity. Mean serum level of MIF was significant higher in new-onset diabetes associated PC patients in comparison with other groups. MIF is up-regulated in patients with pancreatic cancer and causes dysfunction of insulin secretion in β-cells.
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影响因子：
29.4
作者：
Aggarwal G;Ramachandran V;Javeed N;Arumugam T;Dutta S;Klee GG;Klee EW;Smyrk TC;Bamlet W;Han JJ;Rumie Vittar NB;de Andrade M;Mukhopadhyay D;Petersen GM;Fernandez-Zapico ME;Logsdon CD;Chari ST
通讯作者：
Chari ST
影响因子：
15.9
作者：
Benigni, F;Atsumi, T;Bucala, R
通讯作者：
Bucala, R
影响因子：
4.4
作者：
Atsumi, Toshiya;Cho, You-Ree;Bucala, Richard
通讯作者：
Bucala, Richard
影响因子：
11.2
作者：
Kuuselo, Riina;Savinainen, Kimmo;Kallioniemi, Anne
通讯作者：
Kallioniemi, Anne
影响因子：
4
作者：
Serre-Beinier, Veronique;Toso, Christian;Berney, Thierry
通讯作者：
Berney, Thierry