Actin mesh in Re-epithelialization during skin regeneration in adult newt (Cynops pyrrhogaster)

Introduction: Studies have highlighted the role of actin cables in embryonic scarless wound healing across various species. However, evidence for similar structures in adult animals remains lacking. Adult newts, known for their exceptional skin regeneration capabilities, are considered promising mod...

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Main Authors: Yu Liou, Nobuko Moritoki, Tomoko Shindo, Tatsuyuki Ishii, Kazuo Kishi
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Regenerative Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352320425000689
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author Yu Liou
Nobuko Moritoki
Tomoko Shindo
Tatsuyuki Ishii
Kazuo Kishi
author_facet Yu Liou
Nobuko Moritoki
Tomoko Shindo
Tatsuyuki Ishii
Kazuo Kishi
author_sort Yu Liou
collection DOAJ
description Introduction: Studies have highlighted the role of actin cables in embryonic scarless wound healing across various species. However, evidence for similar structures in adult animals remains lacking. Adult newts, known for their exceptional skin regeneration capabilities, are considered promising models for postnatal human studies. This study investigated actin fiber formation and alignment during re-epithelialization in the Japanese fire-bellied newt (Cynops pyrrhogaster). Methods: Full-thickness skin excisions were performed, and actin structures were analyzed using immunohistochemistry and electron microscopy. The role of actin in re-epithelialization was assessed by inhibiting its formation with cytochalasin B. Myosin, an interacting cytoskeletal molecule, was examined through immunohistochemistry, while E-cadherin, an adhesion molecule, was analyzed using both immunohistochemistry and electron microscopy. Results: Rather than an actin cable a mesh-like actin structure, termed the “actin mesh,” was identified via immunohistochemical analysis. The actin mesh developed alongside wound epidermis extension and disappeared following complete re-epithelialization. Inhibition of actin formation delayed re-epithelialization, although the overall healing process showed no significant difference from the control group. Immunohistochemistry revealed the presence of myosin II and E-cadherin alongside Filamentous actin. Electron microscopy further demonstrated actin-rich structures in the wound epidermis compared to normal skin and confirmed E-cadherin-mediated cell-cell adhesion in the wound area. Conclusions: The actin mesh plays a critical role in facilitating rapid re-epithelialization in adult newts, presenting a valuable model for studying scarless wound healing in adult organisms. The involvement of interacting molecules such as myosin and E-cadherin provides insights into the underlying mechanisms of this process. This model offers potential applications for addressing intractable wounds in humans.
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spelling doaj-art-3c75de1203ae4a658f036a08b2f3c2bc2025-08-20T01:51:16ZengElsevierRegenerative Therapy2352-32042025-06-012925426110.1016/j.reth.2025.03.014Actin mesh in Re-epithelialization during skin regeneration in adult newt (Cynops pyrrhogaster)Yu Liou0Nobuko Moritoki1Tomoko Shindo2Tatsuyuki Ishii3Kazuo Kishi4Department of Medical Education, Linkou Chang Gung Memorial Hospital, No.5, Fusing St., Gueishan Township, Taoyuan County 333, TaiwanElectron Microscope Laboratory, Keio University School of Medicine, Shinanomachi 35, Tokyo 160-8582, JapanElectron Microscope Laboratory, Keio University School of Medicine, Shinanomachi 35, Tokyo 160-8582, JapanDepartment of Plastic and Reconstructive Surgery, Keio University School of Medicine, Shinanomachi 35, Tokyo 160-8582, Japan; Corresponding author.Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Shinanomachi 35, Tokyo 160-8582, Japan; Corresponding author.Introduction: Studies have highlighted the role of actin cables in embryonic scarless wound healing across various species. However, evidence for similar structures in adult animals remains lacking. Adult newts, known for their exceptional skin regeneration capabilities, are considered promising models for postnatal human studies. This study investigated actin fiber formation and alignment during re-epithelialization in the Japanese fire-bellied newt (Cynops pyrrhogaster). Methods: Full-thickness skin excisions were performed, and actin structures were analyzed using immunohistochemistry and electron microscopy. The role of actin in re-epithelialization was assessed by inhibiting its formation with cytochalasin B. Myosin, an interacting cytoskeletal molecule, was examined through immunohistochemistry, while E-cadherin, an adhesion molecule, was analyzed using both immunohistochemistry and electron microscopy. Results: Rather than an actin cable a mesh-like actin structure, termed the “actin mesh,” was identified via immunohistochemical analysis. The actin mesh developed alongside wound epidermis extension and disappeared following complete re-epithelialization. Inhibition of actin formation delayed re-epithelialization, although the overall healing process showed no significant difference from the control group. Immunohistochemistry revealed the presence of myosin II and E-cadherin alongside Filamentous actin. Electron microscopy further demonstrated actin-rich structures in the wound epidermis compared to normal skin and confirmed E-cadherin-mediated cell-cell adhesion in the wound area. Conclusions: The actin mesh plays a critical role in facilitating rapid re-epithelialization in adult newts, presenting a valuable model for studying scarless wound healing in adult organisms. The involvement of interacting molecules such as myosin and E-cadherin provides insights into the underlying mechanisms of this process. This model offers potential applications for addressing intractable wounds in humans.http://www.sciencedirect.com/science/article/pii/S2352320425000689RegenerationWound healingRe-epithelializationActinNewt
spellingShingle Yu Liou
Nobuko Moritoki
Tomoko Shindo
Tatsuyuki Ishii
Kazuo Kishi
Actin mesh in Re-epithelialization during skin regeneration in adult newt (Cynops pyrrhogaster)
Regenerative Therapy
Regeneration
Wound healing
Re-epithelialization
Actin
Newt
title Actin mesh in Re-epithelialization during skin regeneration in adult newt (Cynops pyrrhogaster)
title_full Actin mesh in Re-epithelialization during skin regeneration in adult newt (Cynops pyrrhogaster)
title_fullStr Actin mesh in Re-epithelialization during skin regeneration in adult newt (Cynops pyrrhogaster)
title_full_unstemmed Actin mesh in Re-epithelialization during skin regeneration in adult newt (Cynops pyrrhogaster)
title_short Actin mesh in Re-epithelialization during skin regeneration in adult newt (Cynops pyrrhogaster)
title_sort actin mesh in re epithelialization during skin regeneration in adult newt cynops pyrrhogaster
topic Regeneration
Wound healing
Re-epithelialization
Actin
Newt
url http://www.sciencedirect.com/science/article/pii/S2352320425000689
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AT nobukomoritoki actinmeshinreepithelializationduringskinregenerationinadultnewtcynopspyrrhogaster
AT tomokoshindo actinmeshinreepithelializationduringskinregenerationinadultnewtcynopspyrrhogaster
AT tatsuyukiishii actinmeshinreepithelializationduringskinregenerationinadultnewtcynopspyrrhogaster
AT kazuokishi actinmeshinreepithelializationduringskinregenerationinadultnewtcynopspyrrhogaster