Department of Dermatology & Plastic Surgery, Akita University Graduate School of Medicine, Akita, Japan.
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan.
J Dermatol Sci. 2019 Feb;93(2):101-108. doi: 10.1016/j.jdermsci.2019.01.001. Epub 2019 Jan 8.
The epidermis possesses regenerative properties that become apparent only after wounding. Atypical protein kinase C (aPKC) isoforms aPKCζ and aPKCλ form a ternary complex with Par3 and Par6, and play crucial roles in establishing and maintaining epithelial cell polarity. The epidermal loss of aPKCλ results in progressive depletion of hair follicle stem cells. However, it is unclear whether aPKCs have equivalent activities in epidermal regeneration.
To clarify functional differences between aPKCζ and aPKCλ in cutaneous wound healing.
We compared cutaneous wound healing processes in vivo using mutant mice with genetic deletion of each aPKC isoform. We also analyzed functional differences between aPKCζ and aPKCλ in cell proliferation, directional cell migration, and formation of microtubules in vitro using primary keratinocytes established from each mutant mouse.
Wound healing was significantly retarded in epidermis-specific aPKCλ knockout mice. In aPKCλ-deleted keratinocytes, the correct orientation of cell protrusions toward the wound was disrupted through the destabilization of Par6β. The elongation of stabilized β-tubulin was also deteriorated in aPKCλ-deleted keratinocytes, leading to defects in cell spreading. Conversely, wound healing and directional cell migration in aPKCζ-deleted mice were comparable to those in their control littermates.
aPKCs are not functionally equivalent; aPKCλ, but not aPKCζ, plays a primary role in cutaneous wound healing.
表皮具有再生特性，只有在受伤后才会显现出来。非典型蛋白激酶 C（aPKC）同工型 aPKCζ 和 aPKCλ 与 Par3 和 Par6 形成三元复合物，在建立和维持上皮细胞极性方面发挥着关键作用。表皮中 aPKCλ 的缺失会导致毛囊干细胞逐渐耗竭。然而，aPKC 在表皮再生中是否具有等效的活性尚不清楚。
阐明 aPKCζ 和 aPKCλ 在皮肤创伤愈合中的功能差异。
我们使用每种 aPKC 同工型基因缺失的突变小鼠在体内比较了皮肤创伤愈合过程。我们还使用从每种突变小鼠中建立的原代角质形成细胞，在体外分析了 aPKCζ 和 aPKCλ 在细胞增殖、定向细胞迁移和微管形成方面的功能差异。
表皮特异性 aPKCλ 敲除小鼠的伤口愈合明显延迟。在 aPKCλ 缺失的角质形成细胞中，通过 Par6β 的不稳定破坏了细胞突起向伤口的正确定向。稳定的 β-微管的延伸也在 aPKCλ 缺失的角质形成细胞中恶化，导致细胞铺展缺陷。相反，aPKCζ 缺失小鼠的伤口愈合和定向细胞迁移与对照同窝仔鼠相当。
aPKC 并非功能等效；aPKCλ 而非 aPKCζ 在皮肤创伤愈合中起主要作用。
