Ion channel signaling influences cellular proliferation and phagocyte activity during axolotl tail regeneration

Autor: S. Randal Voss, Jeffrey L. Osborn, Brandon M. Franklin
Rok vydání: 2017
Předmět:
Zdroj: Mechanisms of Development. 146:42-54
ISSN: 0925-4773
DOI: 10.1016/j.mod.2017.06.001
Popis: Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, K(V)2.1, K(V)2.2, L-type Ca(V) channels and H/K ATPases) or completely (GlyR, GABA(A)R, K(V)1.5 and SERCA pumps) inhibited tail regeneration. Partial inhibition of tail regeneration by blocking the calcium activated chloride channels, anoctamin1&2, was associated with a reduction of cellular proliferation in tail muscle and mesenchymal regions. Inhibition of anoctamin 1/2 also altered the post-amputation transcriptional response of p44/42 MAPK signaling pathway genes, including decreased expression of erk1/erk2. We also found that complete inhibition via voltage gated K(+) channel blockade was associated with diminished phagocyte recruitment to the amputation site. The identification of H(+) pumps as required for axolotl tail regeneration supports findings in Xenopus and Planaria models, and more generally, the conservation of ion channels as regulators of tissue regeneration. This study provides a preliminary framework for an in-depth investigation of the mechanistic role of ion channels and their potential involvement in regulating cellular proliferation and other processes essential to wound healing, appendage regeneration, and tissue repair.
Databáze: OpenAIRE
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