Abstract
s / Pancreatology 13 (2013) e1–e94 e8 tamoxifen-induced Ela-Cre-ERT2;Yapflox/flox mice resulted in severe (“necrotizing”) pancreatitis, including the onset of mortality, compared to littermates with retained pancreatic Yap expression. Transcriptional profiling confirmed the failure to induce multiple anti-apoptotic molecules, including survivin, in the absence of Yap protein, which was accompanied by an increase in acinar cell apoptosis. However, neither exocrine regeneration itself, nor the upregulation of canonical signaling pathways implicated in regeneration (Notch and Hedgehog), was significantly abrogated in the absence of Yap. Thus, an intact Hippo pathway is essential for pancreatic morphogenesis during embryonic development. While in the mature pancreas, absence of Yap profoundly exacerbates exocrine pancreatitis. Systemic therapeutics directed at negating YAP function in cancer cells need to be cognizant of the requirement for sustained YAP signaling in embryonic and mature tissues.
Published Version
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