Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development.
Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development.
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在产后发育过程中，胰腺外分泌组织的结构和完整性由 E-钙粘蛋白维持。
DOI：
10.1038/s41598-018-31603-2
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发表时间：
2018
影响因子：
4.6
通讯作者：
Shih,HungPing
中科院分区：
文献类型：
--
作者：
Serrill,JeffreyD;Sander,Maike;Shih,HungPing
钙粘蛋白介导的细胞间粘附在器官发育中发挥重要作用，钙粘蛋白表达的变化通常与形态发生和致病事件有关。钙粘蛋白与其他细胞内成分相互作用，形成粘附连接 (AJ) 并在相邻细胞之间提供机械附着。 E-钙粘蛋白 (Cdh1) 是这些细胞间连接的重要组成部分。为了阐明 E-钙粘蛋白在胰腺发育中的功能，我们生成并研究了胰腺特异性 Cdh1 敲除 (Cdh1ΔPan/ΔPan) 小鼠。Cdh1ΔPan/ΔPan 小鼠在出生时表现出正常的体型，但体重未能增加，并在不久后出现低血糖。我们发现，E-钙粘蛋白并不是出生时建立顶端-基底极性或胰腺外分泌细胞身份所必需的。然而，出生后四天，Cdh1ΔPan/ΔPan突变体的胰腺表现出外分泌结构逐渐恶化以及Wnt和YAP信号传导失调。此时，Cdh1ΔPan/ΔPan突变体的腺泡细胞开始表现出导管表型，表明E-钙粘蛋白缺陷的胰腺中存在腺泡到导管化生（ADM）。我们的研究结果表明，E-钙粘蛋白在维持外分泌结构和调节稳态信号传导中发挥着不可或缺的作用。本研究深入了解钙粘蛋白介导的细胞间粘附在胰腺炎或胰腺癌等致病性疾病中的作用。
Cadherin-mediated cell-cell adhesion plays an important role in organ development and changes in cadherin expression are often linked to morphogenetic and pathogenic events. Cadherins interact with other intracellular components to form adherens junctions (AJs) and provide mechanical attachments between adjacent cells. E-cadherin (Cdh1) represents an integral component of these intercellular junctions. To elucidate the function of E-cadherin in the developing pancreas, we generated and studied pancreas-specificCdh1-knockout (Cdh1ΔPan/ΔPan) mice.Cdh1ΔPan/ΔPanmice exhibit normal body size at birth, but fail to gain weight and become hypoglycemic soon afterward. We found that E-cadherin is not required for the establishment of apical-basal polarity or pancreatic exocrine cell identity at birth. However, four days after birth, the pancreata ofCdh1ΔPan/ΔPanmutants display progressive deterioration of exocrine architecture and dysregulation of Wnt and YAP signaling. At this time point, the acinar cells ofCdh1ΔPan/ΔPanmutants begin to exhibit ductal phenotypes, suggesting acinar-to-ductal metaplasia (ADM) in the E-cadherin-deficient pancreas. Our findings demonstrate that E-cadherin plays an integral role in the maintenance of exocrine architecture and regulation of homeostatic signaling. The present study provides insights into the involvement of cadherin-mediated cell-cell adhesion in pathogenic conditions such as pancreatitis or pancreatic cancer.