Takaya Kento, Sunohara Ayano, Aramaki-Hattori Noriko, Sakai Shigeki, Okabe Keisuke, Kishi Kazuo
Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
Biomedicines. 2022 Aug 31;10(9):2132. doi: 10.3390/biomedicines10092132.
Multiple transitions occur in the healing ability of the skin during embryonic development in mice. Embryos up to embryonic day 13 (E13) regenerate completely without a scar after full-thickness wounding. Then, up to E16, dermal structures can be formed, including skin appendages such as hair follicles. However, after E17, wound healing becomes incomplete, and scar formation is triggered. Lhx2 regulates the switch between maintenance and activation of hair follicle stem cells, which are involved in wound healing. Therefore, we investigated the role of Lhx2 in fetal wound healing. Embryos of ICR mice were surgically wounded at E13, E15, and E17, and the expression of Lhx2 along with mitotic (Ki67 and p63) and epidermal differentiation (keratin-10 and loricrin) markers was analyzed. The effect of Lhx2 knockdown on wound healing was observed. Lhx2 expression was not noticed in E13 due to the absence of folliculogenesis but was evident in the epidermal basal layer of E15 and E17 and at the base of E17 wounds, along with Ki67 and p63 expression. Furthermore, Lhx2 knockdown in E15 markedly prolonged wound healing and promoted clear scar formation. Therefore, Lhx2 expression is involved in cell division associated with wound healing and may contribute to scar formation in late embryos.
在小鼠胚胎发育过程中，皮肤的愈合能力会发生多次转变。在胚胎第13天（E13）之前的胚胎，全层受伤后能够完全再生且不留疤痕。然后，直到E16，可以形成真皮结构，包括毛囊等皮肤附属器。然而，在E17之后，伤口愈合变得不完全，并引发疤痕形成。Lhx2调节参与伤口愈合的毛囊干细胞的维持和激活之间的转换。因此，我们研究了Lhx2在胎儿伤口愈合中的作用。对ICR小鼠胚胎在E13、E15和E17进行手术创伤，并分析Lhx2以及有丝分裂（Ki67和p63）和表皮分化（角蛋白-10和兜甲蛋白）标志物的表达。观察了Lhx2敲低对伤口愈合的影响。由于没有毛囊形成，在E13未观察到Lhx2表达，但在E15和E17的表皮基底层以及E17伤口底部，Lhx2表达明显，同时伴有Ki67和p63表达。此外，E15中Lhx2敲低显著延长了伤口愈合时间，并促进了明显的疤痕形成。因此，Lhx2表达参与了与伤口愈合相关的细胞分裂，可能在晚期胚胎的疤痕形成中起作用。
