Early in gestation, wounds in fetal skin heal by regeneration, in which microRNAs play key roles. Seq-915_x4024 is a novel microRNA candidate confirmed by deep sequencing and mirTools 2.0. It is highly expressed in fetal keratinocytes during early gestation. Using an in vitro wound-healing assay, Transwell cell migration assay, and MTS proliferation assay, we demonstrated that keratinocytes overexpressing seq-915_x4024 exhibited higher proliferative activity and the ability to promote fibroblast migration and fibroblast proliferation. These characteristics of keratinocytes are the same biological behaviors as those of fetal keratinocytes, which contribute to skin regeneration. In addition, seq-915_x4024 suppressed the expression of the pro-inflammatory markers TNF-α, IL-6, and IL-8 and the pro-inflammatory chemokines CXCL1 and CXCL5. We also demonstrated that seq-915_x4024 regulates TGF-β isoforms and the extracellular matrix. Moreover, using an in vivo wound-healing model, we demonstrated that overexpression of seq-915_x4024 in keratinocytes suppresses inflammatory cell infiltration and scar formation. Using bioinformatics analyses, luciferase reporter assays, and western blotting, we further demonstrated that Sar1A, Smad2, TNF-α, and IL-8 are direct targets of seq-915_x4024. Furthermore, the expression of phosphorylated Smad2 and Smad3 was reduced by seq-915_x4024. Seq-915_x4024 could be used as an anti-fibrotic factor for the treatment of wound healing.

妊娠早期，胎儿皮肤的伤口通过再生而愈合，其中microRNA发挥了关键作用。Seq-915_x4024是经过深度测序和mirTools 2.0证实的新型microRNA候选物。它在妊娠早期在胎儿角质形成细胞中高表达。使用体外伤口愈合测定法，Transwell细胞迁移测定法，和MTS增殖试验，我们证明了过度表达seq-915_x4024的角质形成细胞表现出更高的增殖活性以及促进成纤维细胞迁移和成纤维细胞增殖的能力。角质形成细胞的这些特性与胎儿角质形成细胞具有相同的生物学行为，这有助于皮肤再生。此外，seq-915_x4024抑制了促炎标记TNF-α，IL-6和IL-8以及促炎趋化因子CXCL1和CXCL5的表达。我们还证明了seq-915_x4024调节TGF-β亚型和细胞外基质。此外，使用体内伤口愈合模型，我们证明了seq-915_x4024在角质形成细胞中的过度表达抑制了炎症细胞浸润和瘢痕形成。使用生物信息学分析，萤光素酶报道测定法，和免疫印迹，我们进一步证实Sar1A，Smad2的，TNF-α和IL-8分别为SEQ-915_x4024的直接靶标。此外，磷酸化的Smad2和Smad3的表达被seq-915_x4024降低。Seq-915_x4024可用作抗纤维化因子治疗伤口愈合。