Takaya Kento, Wang Qi, Imbe Yuka, Nobusue Hiroyuki, Okabe Keisuke, Sakai Shigeki, Aramaki-Hattori Noriko, Hanaoka Kenjiro, Saya Hideyuki, Kishi Kazuo
Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan.
Faculty of Pharmacy, Keio University, Minatoku, Tokyo, Japan.
PLoS One. 2025 Sep 8;20(9):e0331006. doi: 10.1371/journal.pone.0331006. eCollection 2025.
In adult mammals and other highly developed animals, incomplete wound healing, scar formation, and fibrosis occur. No treatment for complete tissue regeneration is currently available. However, in mice, at up to 13 days of gestation, early embryonic wounds regenerate without visible scarring. In mouse fetuses, actin cable formation at the epidermal wound margin contributes to regeneration after wounding; however, the relationship between actin behavior and dermal regeneration or scar formation by myofibroblasts is unknown. In the present study, we observed actin dynamics in the wound dermis of mouse fetuses and investigated fibroblast and alpha-smooth muscle actin (α-SMA) properties involved in the switch between regeneration and scar formation in the dermis. In the wound healing process of mouse fetuses, actomyosin bundles develop and contract in a mesh-like pattern in different parts depending on the developmental stage, i.e., in the dermis of E13 (regeneration) and in the fascia of E15 and later (scar formation). Furthermore, in E13 dermal fibroblasts, α-SMA is present in the cytoplasm independently of actin, but in E15 and later myofibroblasts, TGFβ-1 stimulation causes the distribution of α-SMA and actin to coincide, and in E17, when dermal scarring occurs, α-SMA is expressed particularly in the nucleus. The results indicate that reticular contraction by actomyosin is involved in dermal regeneration, and that the discrepancy in the localization of actin and α-SMA in fibroblasts is necessary. The findings may contribute to effective wound regeneration therapy.
在成年哺乳动物和其他高度发达的动物中，会出现伤口愈合不完全、瘢痕形成和纤维化的情况。目前尚无完全组织再生的治疗方法。然而，在小鼠妊娠至13天时，早期胚胎伤口能够再生且无明显瘢痕形成。在小鼠胎儿中，表皮伤口边缘肌动蛋白丝的形成有助于伤口后的再生；然而，肌动蛋白行为与成肌纤维细胞引起的真皮再生或瘢痕形成之间的关系尚不清楚。在本研究中，我们观察了小鼠胎儿伤口真皮中的肌动蛋白动态，并研究了真皮中参与再生和瘢痕形成转换的成纤维细胞和α-平滑肌肌动蛋白（α-SMA）特性。在小鼠胎儿的伤口愈合过程中，肌动球蛋白束根据发育阶段在不同部位以网状模式发育和收缩，即在E13（再生）的真皮以及E15及之后（瘢痕形成）的筋膜中。此外，在E13真皮成纤维细胞中，α-SMA独立于肌动蛋白存在于细胞质中，但在E15及之后的成肌纤维细胞中，TGFβ-1刺激会导致α-SMA和肌动蛋白的分布重合，而在E17真皮瘢痕形成时，α-SMA尤其在细胞核中表达。结果表明，肌动球蛋白的网状收缩参与真皮再生，并且成纤维细胞中肌动蛋白和α-SMA定位的差异是必要的。这些发现可能有助于有效的伤口再生治疗。
