Inflammatory, proliferative and remodeling phases constitute a cutaneous wound healing program. Therapeutic applications and medication are available; however, they commonly are comprised of fortified preservatives that might prolong the healing process. Chick early amniotic fluids (ceAF) contain native therapeutic factors with balanced chemokines, cytokines and growth-related factors; their origins in principle dictate no existence of harmful agents that would otherwise hamper embryo development. Instead, they possess a spectrum of molecules driving expeditious mitotic divisions and possibly exerting other functions. Employing both in vitro and in vivo models, we examined ceAF's therapeutic potentials in wound healing and found intriguing involvement of transient senescence, known to be intimately intermingled with Senescence Associated Secretory Phenotypes (SASP) that function in addition to or in conjunction with ceAF to facilitate wound healing. In our cutaneous wound healing models, a low dose of ceAF exhibited the best efficacies; however, higher doses attenuated the wound healing presumably by inducing p16 expression over a threshold. Our studies thus link an INK4/ARF locus-mediated signaling cascade to cutaneous wound healing, suggesting therapeutic potentials of ceAF exerting functions likely by driving transient senescence, expediting cellular proliferation, migration, and describing a homeostatic and balanced dosage strategy in medical intervention.

炎症、增殖和重塑阶段构成皮肤伤口愈合程序。治疗应用和药物可用；然而，它们通常由可能延长愈合过程的强化防腐剂组成。雏鸡早期羊水 (ceAF) 含有天然治疗因子，具有平衡的趋化因子、细胞因子和生长相关因子；它们的起源原则上表明不存在会阻碍胚胎发育的有害物质。相反，它们拥有一系列分子，可驱动快速有丝分裂并可能发挥其他功能。采用体外和体内模型中，我们检查了 ceAF 在伤口愈合中的治疗潜力，并发现了短暂衰老的有趣参与，已知与衰老相关分泌表型 (SASP) 密切混合，这些表型在 ceAF 之外或与 ceAF 一起起作用以促进伤口愈合。在我们的皮肤伤口愈合模型中，低剂量的 ceAF 表现出最佳效果；然而，较高的剂量可能通过诱导 p16 表达超过阈值来减弱伤口愈合。因此，我们的研究将 INK4/ARF 基因座介导的信号级联与皮肤伤口愈合联系起来，表明 ceAF 的治疗潜力可能通过驱动短暂衰老、加速细胞增殖、迁移和描述医疗干预中的稳态和平衡剂量策略发挥作用。