Zhang Wengeng, Das Pragnya, Kelangi Sarah, Bei Marianna
Center for Engineering in Medicine, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114, USA.
Shriners Hospital for Children, Boston, MA 02114, USA.
Precis Clin Med. 2020 Mar;3(1):22-33. doi: 10.1093/pcmedi/pbz029. Epub 2019 Dec 30.
Ion channels are a large family of transmembrane proteins, accessible by soluble membrane-impermeable molecules, and thus are targets for development of therapeutic drugs. Ion channels are the second most common target for existing drugs, after G protein-coupled receptors, and are expected to make a big impact on precision medicine in many different diseases including wound repair and regeneration. Research has shown that endogenous bioelectric signaling mediated by ion channels is critical in non-mammalian limb regeneration. However, the role of ion channels in regeneration of limbs in mammalian systems is not yet defined.
To explore the role of potassium channels in limb wound repair and regeneration, the hindlimbs of mouse embryos were amputated at E12.5 when the wound is expected to regenerate and E15.5 when the wound is not expected to regenerate, and gene expression of potassium channels was studied.
Most of the potassium channels were downregulated, except for the potassium channel (Kir6.1) which was upregulated in E12.5 embryos after amputation.
This study provides a new mouse limb regeneration model and demonstrates that potassium channels are potential drug targets for limb wound healing and regeneration.
离子通道是一大类跨膜蛋白，可被不能透过膜的可溶性分子作用，因此是治疗药物开发的靶点。离子通道是现有药物的第二大常见靶点，仅次于G蛋白偶联受体，预计在包括伤口修复和再生在内的许多不同疾病的精准医学中发挥重大作用。研究表明，离子通道介导的内源性生物电信号在非哺乳动物肢体再生中至关重要。然而，离子通道在哺乳动物系统肢体再生中的作用尚未明确。
为探究钾通道在肢体伤口修复和再生中的作用，在预期伤口会再生的胚胎期12.5天和预期伤口不会再生的胚胎期15.5天对小鼠胚胎的后肢进行截肢，并研究钾通道的基因表达。
除了钾通道Kir6.1在截肢后的胚胎期12.5天上调外，大多数钾通道下调。
本研究提供了一种新的小鼠肢体再生模型，并证明钾通道是肢体伤口愈合和再生的潜在药物靶点。
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