Effect of All-trans Retinoic Acid on Panniculus Carnosus Muscle Regeneration in Fetal Mouse Wound Healing

Background:. The dermal panniculus carnosus (PC) muscle is critical for wound contraction in lower mammals and is a useful model of muscle regeneration owing to its high cellular metabolic turnover. During wound healing in mice, skin structures, including PC, are completely regenerated up to embryon...

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Main Authors: Kento Takaya, MD, Noriko Aramaki-Hattori, MD, PhD, Shigeki Sakai, MD, PhD, Keisuke Okabe, MD, PhD, Toru Asou, PD, PhD, Kazuo Kishi, MD, PhD
Format: Article
Language:English
Published: Wolters Kluwer 2022-09-01
Series:Plastic and Reconstructive Surgery, Global Open
Online Access:http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000004533
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author Kento Takaya, MD
Noriko Aramaki-Hattori, MD, PhD
Shigeki Sakai, MD, PhD
Keisuke Okabe, MD, PhD
Toru Asou, PD, PhD
Kazuo Kishi, MD, PhD
author_facet Kento Takaya, MD
Noriko Aramaki-Hattori, MD, PhD
Shigeki Sakai, MD, PhD
Keisuke Okabe, MD, PhD
Toru Asou, PD, PhD
Kazuo Kishi, MD, PhD
author_sort Kento Takaya, MD
collection DOAJ
description Background:. The dermal panniculus carnosus (PC) muscle is critical for wound contraction in lower mammals and is a useful model of muscle regeneration owing to its high cellular metabolic turnover. During wound healing in mice, skin structures, including PC, are completely regenerated up to embryonic day (E) 13, but PC is only partially regenerated in fetuses or adult animals after E14. Nevertheless, the mechanisms underlying wound repair for complete regeneration in PC have not been fully elucidated. We hypothesized that retinoic acid (RA) signaling, which is involved in muscle differentiation, regulates PC regeneration. Methods:. Surgical injury was induced in ICR mice on E13 and E14. RA receptor alpha (RARα) expression in tissue samples from embryos was evaluated using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. To evaluate the effects of RA on PC regeneration, beads soaked in all-trans RA (ATRA) were implanted in E13 wounds, and tissues were observed. The effects of RA on myoblast migration were evaluated using a cell migration assay. Results:. During wound healing, RARα expression was enhanced at the cut surface in PCs of E13 wounds but was attenuated at the cut edge of E14 PCs. Implantation of ATRA-containing beads inhibited PC regeneration on E13 in a concentration-dependent manner. Treatment of myoblasts with ATRA inhibited cell migration. Conclusions:. ATRA inhibits PC regeneration, and decreased RARα expression in wounds after E14 inhibits myoblast migration. Our findings may contribute to the development of therapies to promote complete wound regeneration, even in the muscle.
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spelling doaj.art-1835457d09054d4da0f1bc95bca97bd82022-12-22T03:53:46ZengWolters KluwerPlastic and Reconstructive Surgery, Global Open2169-75742022-09-01109e453310.1097/GOX.0000000000004533202209000-00034Effect of All-trans Retinoic Acid on Panniculus Carnosus Muscle Regeneration in Fetal Mouse Wound HealingKento Takaya, MD0Noriko Aramaki-Hattori, MD, PhD1Shigeki Sakai, MD, PhD2Keisuke Okabe, MD, PhD3Toru Asou, PD, PhD4Kazuo Kishi, MD, PhD5From the Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, Japan.From the Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, Japan.From the Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, Japan.From the Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, Japan.From the Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, Japan.From the Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, Japan.Background:. The dermal panniculus carnosus (PC) muscle is critical for wound contraction in lower mammals and is a useful model of muscle regeneration owing to its high cellular metabolic turnover. During wound healing in mice, skin structures, including PC, are completely regenerated up to embryonic day (E) 13, but PC is only partially regenerated in fetuses or adult animals after E14. Nevertheless, the mechanisms underlying wound repair for complete regeneration in PC have not been fully elucidated. We hypothesized that retinoic acid (RA) signaling, which is involved in muscle differentiation, regulates PC regeneration. Methods:. Surgical injury was induced in ICR mice on E13 and E14. RA receptor alpha (RARα) expression in tissue samples from embryos was evaluated using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. To evaluate the effects of RA on PC regeneration, beads soaked in all-trans RA (ATRA) were implanted in E13 wounds, and tissues were observed. The effects of RA on myoblast migration were evaluated using a cell migration assay. Results:. During wound healing, RARα expression was enhanced at the cut surface in PCs of E13 wounds but was attenuated at the cut edge of E14 PCs. Implantation of ATRA-containing beads inhibited PC regeneration on E13 in a concentration-dependent manner. Treatment of myoblasts with ATRA inhibited cell migration. Conclusions:. ATRA inhibits PC regeneration, and decreased RARα expression in wounds after E14 inhibits myoblast migration. Our findings may contribute to the development of therapies to promote complete wound regeneration, even in the muscle.http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000004533
spellingShingle Kento Takaya, MD
Noriko Aramaki-Hattori, MD, PhD
Shigeki Sakai, MD, PhD
Keisuke Okabe, MD, PhD
Toru Asou, PD, PhD
Kazuo Kishi, MD, PhD
Effect of All-trans Retinoic Acid on Panniculus Carnosus Muscle Regeneration in Fetal Mouse Wound Healing
Plastic and Reconstructive Surgery, Global Open
title Effect of All-trans Retinoic Acid on Panniculus Carnosus Muscle Regeneration in Fetal Mouse Wound Healing
title_full Effect of All-trans Retinoic Acid on Panniculus Carnosus Muscle Regeneration in Fetal Mouse Wound Healing
title_fullStr Effect of All-trans Retinoic Acid on Panniculus Carnosus Muscle Regeneration in Fetal Mouse Wound Healing
title_full_unstemmed Effect of All-trans Retinoic Acid on Panniculus Carnosus Muscle Regeneration in Fetal Mouse Wound Healing
title_short Effect of All-trans Retinoic Acid on Panniculus Carnosus Muscle Regeneration in Fetal Mouse Wound Healing
title_sort effect of all trans retinoic acid on panniculus carnosus muscle regeneration in fetal mouse wound healing
url http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000004533
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