Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjukuku, Tokyo, 160-8582, Japan.
Faculty of Pharmacy, Keio University, Shiba, Minatoku, Tokyo, Japan.
Sci Rep. 2022 Sep 23;12(1):15913. doi: 10.1038/s41598-022-18175-y.
Up to a certain developmental stage, a fetus can completely regenerate wounds in the skin. To clarify the mechanism of fetal skin regeneration, identifying when the skin switches from fetal-type wound regeneration to adult-type wound repair is necessary. We hypothesized that this switch occurs at several time points and that complete skin regeneration requires epidermal-dermal interactions and the formation of actin cables. We compared normal skin and wound morphology at each developmental stage. We examined two parameters: epidermal texture and dermal structure. We found that the three-dimensional structure of the skin was completely regenerated in full-thickness skin incisions made before embryonic day (E) 13. However, the skin texture did not regenerate in wounds made after E14. We also found that the dermal structure regenerates up to E16, but wounds created after E17 heal as scars with dermal fibrosis. By controlling the activity of AMP-activated protein kinase and altering actin cable formation, we could regulate scar formation in utero. These findings may contribute to therapies that allow complete skin regeneration without scarring.
在一定的发育阶段，胎儿可以完全再生皮肤的伤口。为了阐明胎儿皮肤再生的机制，有必要确定皮肤何时从胎儿型伤口再生转变为成人型伤口修复。我们假设这种转变发生在几个时间点，并且完整的皮肤再生需要表皮-真皮相互作用和肌动蛋白电缆的形成。我们比较了每个发育阶段的正常皮肤和伤口形态。我们检查了两个参数：表皮纹理和真皮结构。我们发现，在胚胎第 13 天（E）之前进行的全层皮肤切口可以完全再生皮肤的三维结构。然而，在 E14 之后进行的伤口中，皮肤纹理不会再生。我们还发现，真皮结构可再生至 E16，但在 E17 之后形成的伤口会形成带有真皮纤维化的疤痕。通过控制 AMP 激活蛋白激酶的活性和改变肌动蛋白电缆的形成，我们可以在子宫内调节疤痕形成。这些发现可能有助于实现无疤痕的完整皮肤再生治疗。
