School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea.
Institute of Life Science and Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea.
Sci Rep. 2024 May 14;14(1):10978. doi: 10.1038/s41598-024-61674-3.
Maintaining epidermal homeostasis relies on a tightly organized process of proliferation and differentiation of keratinocytes. While past studies have primarily focused on calcium regulation in keratinocyte differentiation, recent research has shed light on the crucial role of lysosome dysfunction in this process. TLR adaptor interacting with SLC15A4 on the lysosome (TASL) plays a role in regulating pH within the endo-lysosome. However, the specific role of TASL in keratinocyte differentiation and its potential impact on proliferation remains elusive. In our study, we discovered that TASL deficiency hinders the proliferation and migration of keratinocytes by inducing G1/S cell cycle arrest. Also, TASL deficiency disrupts proper differentiation process in TASL knockout human keratinocyte cell line (HaCaT) by affecting lysosomal function. Additionally, our research into calcium-induced differentiation showed that TASL deficiency affects calcium modulation, which is essential for keratinocyte regulation. These findings unveil a novel role of TASL in the proliferation and differentiation of keratinocytes, providing new insights into the intricate regulatory mechanisms of keratinocyte biology.
维持表皮稳态依赖于角质形成细胞增殖和分化的紧密组织过程。虽然过去的研究主要集中在角质形成细胞分化中的钙调节，但最近的研究揭示了溶酶体功能障碍在这一过程中的关键作用。溶酶体上 TLR 衔接蛋白与 SLC15A4 的相互作用（TASL）在调节内溶酶体中的 pH 值方面发挥作用。然而，TASL 在角质形成细胞分化中的具体作用及其对增殖的潜在影响仍不清楚。在我们的研究中，我们发现 TASL 缺乏通过诱导 G1/S 细胞周期停滞来阻碍角质形成细胞的增殖和迁移。此外，TASL 缺乏通过影响溶酶体功能破坏 TASL 敲除人角质形成细胞系（HaCaT）中的适当分化过程。此外，我们对钙诱导分化的研究表明，TASL 缺乏会影响钙调节，这对于角质形成细胞的调节至关重要。这些发现揭示了 TASL 在角质形成细胞增殖和分化中的新作用，为角质形成细胞生物学的复杂调节机制提供了新的见解。
