Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration
Abstract In animal species that have the capability of regenerating tissues and limbs, cell proliferation is enhanced after wound healing and is essential for the reconstruction of injured tissue. Although the ability to induce cell proliferation is a common feature of such species, the molecular me...
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Nature Portfolio
2024-02-01
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Online Access: | https://doi.org/10.1038/s41598-024-54280-w |
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author | Makoto Nakamura Tatsuya Kyoda Hitoshi Yoshida Kimiko Takebayashi-Suzuki Ryota Koike Eri Takahashi Yuka Moriyama Marcin Wlizla Marko E. Horb Atsushi Suzuki |
author_facet | Makoto Nakamura Tatsuya Kyoda Hitoshi Yoshida Kimiko Takebayashi-Suzuki Ryota Koike Eri Takahashi Yuka Moriyama Marcin Wlizla Marko E. Horb Atsushi Suzuki |
author_sort | Makoto Nakamura |
collection | DOAJ |
description | Abstract In animal species that have the capability of regenerating tissues and limbs, cell proliferation is enhanced after wound healing and is essential for the reconstruction of injured tissue. Although the ability to induce cell proliferation is a common feature of such species, the molecular mechanisms that regulate the transition from wound healing to regenerative cell proliferation remain unclear. Here, we show that upon injury, InhibinβA and JunB cooperatively function for this transition during Xenopus tadpole tail regeneration. We found that the expression of inhibin subunit beta A (inhba) and junB proto-oncogene (junb) is induced by injury-activated TGF-β/Smad and MEK/ERK signaling in regenerating tails. Similarly to junb knockout (KO) tadpoles, inhba KO tadpoles show a delay in tail regeneration, and inhba/junb double KO (DKO) tadpoles exhibit severe impairment of tail regeneration compared with either inhba KO or junb KO tadpoles. Importantly, this impairment is associated with a significant reduction of cell proliferation in regenerating tissue. Moreover, JunB regulates tail regeneration via FGF signaling, while InhibinβA likely acts through different mechanisms. These results demonstrate that the cooperation of injury-induced InhibinβA and JunB is critical for regenerative cell proliferation, which is necessary for re-outgrowth of regenerating Xenopus tadpole tails. |
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issn | 2045-2322 |
language | English |
last_indexed | 2024-03-07T15:05:33Z |
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spelling | doaj.art-b0b3d27a56314054bdc0fb97996d67212024-03-05T18:55:31ZengNature PortfolioScientific Reports2045-23222024-02-0114111210.1038/s41598-024-54280-wInjury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regenerationMakoto Nakamura0Tatsuya Kyoda1Hitoshi Yoshida2Kimiko Takebayashi-Suzuki3Ryota Koike4Eri Takahashi5Yuka Moriyama6Marcin Wlizla7Marko E. Horb8Atsushi Suzuki9Amphibian Research Center, Graduate School of Integrated Sciences for Life, Hiroshima UniversityAmphibian Research Center, Graduate School of Integrated Sciences for Life, Hiroshima UniversityNational Xenopus Resource and Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological LaboratoryAmphibian Research Center, Graduate School of Integrated Sciences for Life, Hiroshima UniversityAmphibian Research Center, Graduate School of Integrated Sciences for Life, Hiroshima UniversityAmphibian Research Center, Graduate School of Integrated Sciences for Life, Hiroshima UniversityAmphibian Research Center, Graduate School of Integrated Sciences for Life, Hiroshima UniversityNational Xenopus Resource and Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological LaboratoryNational Xenopus Resource and Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological LaboratoryAmphibian Research Center, Graduate School of Integrated Sciences for Life, Hiroshima UniversityAbstract In animal species that have the capability of regenerating tissues and limbs, cell proliferation is enhanced after wound healing and is essential for the reconstruction of injured tissue. Although the ability to induce cell proliferation is a common feature of such species, the molecular mechanisms that regulate the transition from wound healing to regenerative cell proliferation remain unclear. Here, we show that upon injury, InhibinβA and JunB cooperatively function for this transition during Xenopus tadpole tail regeneration. We found that the expression of inhibin subunit beta A (inhba) and junB proto-oncogene (junb) is induced by injury-activated TGF-β/Smad and MEK/ERK signaling in regenerating tails. Similarly to junb knockout (KO) tadpoles, inhba KO tadpoles show a delay in tail regeneration, and inhba/junb double KO (DKO) tadpoles exhibit severe impairment of tail regeneration compared with either inhba KO or junb KO tadpoles. Importantly, this impairment is associated with a significant reduction of cell proliferation in regenerating tissue. Moreover, JunB regulates tail regeneration via FGF signaling, while InhibinβA likely acts through different mechanisms. These results demonstrate that the cooperation of injury-induced InhibinβA and JunB is critical for regenerative cell proliferation, which is necessary for re-outgrowth of regenerating Xenopus tadpole tails.https://doi.org/10.1038/s41598-024-54280-wInhibinβAJunBFGFXenopus tail regenerationRegenerative cell proliferation |
spellingShingle | Makoto Nakamura Tatsuya Kyoda Hitoshi Yoshida Kimiko Takebayashi-Suzuki Ryota Koike Eri Takahashi Yuka Moriyama Marcin Wlizla Marko E. Horb Atsushi Suzuki Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration Scientific Reports InhibinβA JunB FGF Xenopus tail regeneration Regenerative cell proliferation |
title | Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration |
title_full | Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration |
title_fullStr | Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration |
title_full_unstemmed | Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration |
title_short | Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration |
title_sort | injury induced cooperation of inhibinβa and junb is essential for cell proliferation in xenopus tadpole tail regeneration |
topic | InhibinβA JunB FGF Xenopus tail regeneration Regenerative cell proliferation |
url | https://doi.org/10.1038/s41598-024-54280-w |
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