P21 deficiency delays regeneration of skeletal muscular tissue.
The potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0125765 |
| _version_ | 1818394779976728576 |
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| author | Nobuaki Chinzei Shinya Hayashi Takeshi Ueha Takaaki Fujishiro Noriyuki Kanzaki Shingo Hashimoto Shuhei Sakata Shinsuke Kihara Masahiko Haneda Yoshitada Sakai Ryosuke Kuroda Masahiro Kurosaka |
| author_facet | Nobuaki Chinzei Shinya Hayashi Takeshi Ueha Takaaki Fujishiro Noriyuki Kanzaki Shingo Hashimoto Shuhei Sakata Shinsuke Kihara Masahiko Haneda Yoshitada Sakai Ryosuke Kuroda Masahiro Kurosaka |
| author_sort | Nobuaki Chinzei |
| collection | DOAJ |
| description | The potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model was recreated by intramuscular injection of bupivacaine hydrochloride in the soleus of p21 knockout (KO) mice and wild type (WT) mice. The mice were sacrificed at 3, 14, and 28 days post-operation. The results of hematoxylin-eosin staining and immunofluorescence of muscle membrane indicated that muscle regeneration was delayed in p21 KO mice. Cyclin D1 mRNA expression and both Ki-67 and PCNA immunohistochemistry suggested that p21 deficiency increased cell cycle and muscle cell proliferation. F4/80 immunohistochemistry also suggested the increase of immune response in p21 KO mice. On the other hand, both the mRNA expression and western blot analysis of MyoD, myogenin, and Pax7 indicated that muscular differentiation was delayed in p21KO mice. Considering these results, we confirmed that muscle injury causes an increase in cell proliferation. However, muscle differentiation in p21 KO mice was inhibited due to the low expression of muscular synthesis genes, leading to a delay in the muscular regeneration. Thus, we conclude that p21 plays an important role in the in vivo healing process in muscular injury. |
| first_indexed | 2024-12-14T06:06:38Z |
| format | Article |
| id | doaj.art-3a2d35307557435abb91ee493871478b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T06:06:38Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3a2d35307557435abb91ee493871478b2022-12-21T23:14:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012576510.1371/journal.pone.0125765P21 deficiency delays regeneration of skeletal muscular tissue.Nobuaki ChinzeiShinya HayashiTakeshi UehaTakaaki FujishiroNoriyuki KanzakiShingo HashimotoShuhei SakataShinsuke KiharaMasahiko HanedaYoshitada SakaiRyosuke KurodaMasahiro KurosakaThe potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model was recreated by intramuscular injection of bupivacaine hydrochloride in the soleus of p21 knockout (KO) mice and wild type (WT) mice. The mice were sacrificed at 3, 14, and 28 days post-operation. The results of hematoxylin-eosin staining and immunofluorescence of muscle membrane indicated that muscle regeneration was delayed in p21 KO mice. Cyclin D1 mRNA expression and both Ki-67 and PCNA immunohistochemistry suggested that p21 deficiency increased cell cycle and muscle cell proliferation. F4/80 immunohistochemistry also suggested the increase of immune response in p21 KO mice. On the other hand, both the mRNA expression and western blot analysis of MyoD, myogenin, and Pax7 indicated that muscular differentiation was delayed in p21KO mice. Considering these results, we confirmed that muscle injury causes an increase in cell proliferation. However, muscle differentiation in p21 KO mice was inhibited due to the low expression of muscular synthesis genes, leading to a delay in the muscular regeneration. Thus, we conclude that p21 plays an important role in the in vivo healing process in muscular injury.https://doi.org/10.1371/journal.pone.0125765 |
| spellingShingle | Nobuaki Chinzei Shinya Hayashi Takeshi Ueha Takaaki Fujishiro Noriyuki Kanzaki Shingo Hashimoto Shuhei Sakata Shinsuke Kihara Masahiko Haneda Yoshitada Sakai Ryosuke Kuroda Masahiro Kurosaka P21 deficiency delays regeneration of skeletal muscular tissue. PLoS ONE |
| title | P21 deficiency delays regeneration of skeletal muscular tissue. |
| title_full | P21 deficiency delays regeneration of skeletal muscular tissue. |
| title_fullStr | P21 deficiency delays regeneration of skeletal muscular tissue. |
| title_full_unstemmed | P21 deficiency delays regeneration of skeletal muscular tissue. |
| title_short | P21 deficiency delays regeneration of skeletal muscular tissue. |
| title_sort | p21 deficiency delays regeneration of skeletal muscular tissue |
| url | https://doi.org/10.1371/journal.pone.0125765 |
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