β cells can be generated from cytokeratin 5-positive cells after cerulein-induced pancreatitis in adult mice.
β cells can be generated from cytokeratin 5-positive cells after cerulein-induced pancreatitis in adult mice.
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DOI：
10.1016/j.bbrc.2018.01.008
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发表时间：
2018-01
影响因子：
3.1
通讯作者：
Qiao Shi;Yu-pu Hong;Xiao-yi Zhang;Jing Tao;Chen-yang Wang;Liang Zhao;Fangchao Mei;Yun-dong You
中科院分区：
文献类型：
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作者：
Qiao Shi;Yu-pu Hong;Xiao-yi Zhang;Jing Tao;Chen-yang Wang;Liang Zhao;Fangchao Mei;Yun-dong You
临床研究发现，部分急性胰腺炎（AP）患者在恢复期会出现糖耐量异常，这表明研究恢复胰岛β细胞功能的潜在治疗方法的重要性。细胞角蛋白5（Krt 5）阳性细胞被认为在损伤后肺和唾液腺的再生中起干细胞或祖细胞的作用。本研究采用连续4 d腹腔注射雨蛙肽（100 μg/kg），每6 h 1次的方法，建立急性胰腺炎（AP）模型，以探讨Krt 5阳性细胞在胰腺再生，尤其是β细胞功能恢复中的作用及其机制。结果表明，在AP后恢复过程中，葡萄糖稳态部分恶化。此外，Krt 5阳性细胞簇在受损胰腺中显著增加，其标记为炎性细胞浸润和腺泡细胞根除。此外，在雨蛙肽给药后的损伤区域中发现了胰岛素和Krt 5共标记的细胞，这些细胞中的一部分是GLUT 2免疫阳性的。综上所述，我们的数据表明，Krt 5表达细胞可能参与成年小鼠胰腺的自然自愈过程和AP后β细胞的更新。促进Krt 5表达细胞转化为功能性β细胞可能是减轻体内AP后糖尿病发展的新方法。
Clinical studies have revealed that some patients will develop glucose tolerance dysfunction after recovering from acute pancreatitis (AP), which indicated the importance of investigating the potential therapies for restoration of islet β cell function. Cytokeratin 5 (Krt5)-positive cells are considered to function as stem or progenitor cells in the regeneration of lung and salivary gland following injury. In the present study, AP was induced by six hourly intraperitoneal injections of 100 μg/kg cerulein for 4 consecutive days in adult mice, in order to determine the role of Krt5-positive cells in pancreatic regeneration, especially in the restoration of β cell function and the underlying mechanisms. Results showed that glucose homeostasis were deteriorated partly during the recovery process after AP. Furthermore, clusters of Krt5-positive cells were significantly increased in the damaged pancreas marked by inflammatory cells infiltration and acinar cell eradication. In addition, cells co-labelling insulin and Krt5 were found in the injured region after cerulein administration, part of these cells were immunopositive for GLUT2. Taken together, our data demonstrated that Krt5-expressing cells could be involved in the natural pancreas self-healing process and the renewal of β cells after AP in adult mice. It is promising that promoting conversion of Krt5-expressing cells into functional β cells may be a novel method to mitigate the development of diabetes mellitus after AP in vivo.