Aquaporin-7 and aquaporin-12 modulate the inflammatory phenotype of endocrine pancreatic beta-cells
Aquaporin-7 and aquaporin-12 modulate the inflammatory phenotype of endocrine pancreatic beta-cells
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DOI：
10.1016/j.abb.2020.108481
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发表时间：
2020-09-30
影响因子：
3.9
通讯作者：
Soveral, Graca
中科院分区：
文献类型：
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作者：
da Silva, Ines Vieira;Cardoso, Carlos;Soveral, Graca
水通道蛋白 (AQP) 促进水和甘油跨膜移动。 AQP7 是胰腺 β 细胞中主要的水甘油孔蛋白，被认为在胰岛素胞吐作用中发挥作用。尽管 AQP7 缺失小鼠表现出成年肥胖、胰岛素分泌受损和胰岛素抵抗，但人类 AQP7 功能丧失纯合突变与肥胖或 2 型糖尿病无关。此外，AQP12 在胰腺炎中表达上调。然而，这种亚型在内分泌胰腺炎症中的意义仍不清楚。在这里，我们使用 RIN-m5F β 细胞（一种广泛用于高胰岛素分泌的模型）研究了 AQP7 和 AQP12 在细胞和炎症过程中的参与。 AQP7和AQP12表达与细胞增殖、粘附和迁移直接相关。虽然肿瘤坏死因子-α (TNF α) 诱导的炎症会损害 AQP7 表达并大幅减少胰岛素分泌，但脂多糖 (LPS) 会促进 AQP7 上调，并且 TNF α 和 LPS 都会上调 AQP12。重要的是，过度表达 AQP12 的细胞对炎症具有更强的抵抗力，显示出较低水平的促炎标记物。总而言之，这些数据记录了 AQP7 参与胰岛素分泌和 AQP12 参与炎症，强调了它们在胰腺 β 细胞功能中的基本作用。
Aquaporins (AQPs) facilitate water and glycerol movement across membranes. AQP7 is the main aquaglyceroporin in pancreatic beta-cells and was proposed to play a role in insulin exocytosis. Although AQP7-null mice display adult-onset obesity, impaired insulin secretion and insulin resistance, AQP7 loss-of-function homozygous mutations in humans do not correlate with obesity nor type-2 diabetes. In addition, AQP12 is upregulated in pancreatitis. However, the implication of this isoform in endocrine pancreas inflammation is still unclear. Here, we investigated AQP7 and AQP12 involvement in cellular and inflammatory processes using RIN-m5F beta cells, a model widely used for their high insulin secretion. AQP7 and AQP12 expression were directly associated with cell proliferation, adhesion and migration. While tumor necrosis factor-alpha (TNF alpha)-induced inflammation impaired AQP7 expression and drastically reduced insulin secretion, lipopolysaccharides (LPS) prompted AQP7 upregulation, and both TNF alpha and LPS upregulated AQP12. Importantly, cells overexpressing AQP12 are more resistant to inflammation, revealing lower levels of proinflammatory markers. Altogether, these data document AQP7 involvement in insulin secretion and AQP12 implication in inflammation, highlighting their fundamental role in pancreatic beta-cell function.