Hif1α 缺失通过实验性胰腺炎中异常 B 细胞积累限制组织再生。
Hif1α Deletion Limits Tissue Regeneration via Aberrant B Cell Accumulation in Experimental Pancreatitis.
机构信息
Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Cell Rep. 2018 Jun 19;23(12):3457-3464. doi: 10.1016/j.celrep.2018.05.071.
Pancreatitis is an inflammatory disease of the exocrine pancreas and ranks among the most common gastrointestinal disorders. Inflamed tissues frequently experience conditions of insufficient oxygen availability, or hypoxia. Here, we demonstrate that hypoxia and consequent stabilization of the hypoxia-inducible factor 1α (HIF1α) transcription factor occur in murine and human pancreatitis. Mice lacking pancreas-specific HIF1α expression display markedly impaired pancreatic regeneration following cerulein-induced pancreatitis, which is associated with excessive intrapancreatic B cell accumulation. Notably, B cell depletion in mice with established pancreatitis significantly enhances tissue regeneration. Our study reveals a crosstalk between pancreatic HIF1α expression and B cell trafficking that regulates tissue regeneration, and identifies plausible molecular targets for treating pancreatitis patients.
胰腺炎是一种胰腺外分泌腺的炎症性疾病，属于最常见的胃肠道疾病之一。发炎组织通常会出现供氧不足或缺氧的情况。在这里，我们证明了缺氧以及随之而来的缺氧诱导因子 1α（HIF1α）转录因子的稳定存在于鼠类和人类的胰腺炎中。缺乏胰腺特异性 HIF1α 表达的小鼠在鹅去氧胆酸诱导的胰腺炎后表现出明显受损的胰腺再生，这与胰腺内 B 细胞过度积聚有关。值得注意的是，在已发生胰腺炎的小鼠中耗尽 B 细胞可显著增强组织再生。我们的研究揭示了胰腺 HIF1α 表达与 B 细胞迁移之间的相互作用，这种相互作用调节组织再生，并确定了治疗胰腺炎患者的潜在分子靶点。
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