PDF(Pubmed)
Abstract：
The skin is a multifunctional organ, forming a barrier between the external and internal environment, thereby functioning as a safeguard against extrinsic factors. Autophagy has been implicated in epidermal differentiation and in preserving skin homeostasis. LC3-associated phagocytosis (LAP) uses some but not all components of autophagy. The Atg16l1 (Δ WD) mouse model lacks the WD40 domain required for LAP and has been widely used to study the effects of LAP deficiency and autophagy on tissue homeostasis and response to infection. In this study, the Δ WD model was used to study the relationship between LAP and skin homeostasis by determining whether LAP-deficient mice display a cutaneous phenotype. Skin histology of wild-type and Δ WD mice aged 1 year revealed minor morphological differences in the tail skin dermal layer. RT-qPCR and western blot analysis showed no differences in key keratin expression between genotypes. Skin barrier formation, assessed by dye permeation assays, demonstrated full and proper formation of the skin barrier at embryonic day 18.5 in both genotypes. Biomechanical analysis of the skin showed decreased skin elasticity in aged Δ WD but not wild-type mice. In summary, the LAP-deficient Δ WD mice displayed subtle alterations in dermal histology and age-related biomechanical changes.
摘要：
皮肤是一个多功能的器官,在外部环境和内部环境之间形成屏障，从而起到防范外在因素的作用。自噬与表皮分化和保持皮肤稳态有关。LC3相关吞噬作用（LAP）使用自噬的一些但不是所有成分。Atg16l1（ΔWD）小鼠模型缺乏LAP所需的WD40结构域，已被广泛用于研究LAP缺乏和自噬对组织稳态和感染反应的影响。在这项研究中,ΔWD模型用于通过确定LAP缺陷小鼠是否表现出皮肤表型来研究LAP与皮肤稳态之间的关系。1岁的野生型和ΔWD小鼠的皮肤组织学显示，尾巴皮肤真皮层的形态差异很小。RT-qPCR和蛋白质印迹分析显示基因型之间关键角蛋白表达没有差异。皮肤屏障形成,通过染料渗透试验评估，在两种基因型中，在胚胎第18.5天都显示出皮肤屏障的完全和适当的形成。皮肤的生物力学分析表明，衰老的ΔWD小鼠的皮肤弹性降低，但野生型小鼠则没有。总之,缺乏LAP的ΔWD小鼠在真皮组织学和年龄相关的生物力学变化方面表现出细微的改变。
