Department of Dermatology, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
Department of Medicine, Graduate School, Chung-Ang University, Seoul 06973, Republic of Korea.
J Microbiol Biotechnol. 2024 Sep 28;34(9):1810-1818. doi: 10.4014/jmb.2406.06015. Epub 2024 Jul 26.
Autophagy is essential for regulating hair growth. Accordingly, we developed autophagy activator ICP5249 (pentasodium tetracarboxymethyl palmitoyl dipeptide) and investigated its potential role in hair growth. We evaluated its effect on hair growth using human dermal papilla cells (hDPCs) culture model, human hair follicles (hHFs) organ culture model, and telogenic mouse model. ICP5249 increased hDPCs proliferation and alkaline phosphatase (ALP) expression. It also increased microtubule-associated protein (MAP) light chain 3-II (LC3-II) expression and AMP-activated protein kinase α (AMPKα) and unc-51-like kinase 1 (ULK1) phosphorylation in hDPCs. ICP5249 extended the length of hHFs and increased LC3-II please revised from LC3 II to LC3-II in all manuscript expression. Consistently, ICP5249 also significantly increased hair growth area, dermis thickness, and anagen and telogen ratio in telogenic mice. Furthermore, it upregulated Ki-67 and LC3-II expression and AMPKα phosphorylation on the mice’s dorsal skin. To investigate whether AMPK regulates ICP5249-induced hair growth, following treatment with the compound C, AMPK inhibitor, the activity of ICP5249 was evaluated. The effects of ICP5249 on hair growth were assessed following pretreatment with the AMPK inhibitor compound C. The results showed that compound C suppressed ICP5249-mediated proliferation and hair inductivity in hDPCs. Additionally, compound C inhibited ICP5249-mediated hair growth area, dermis thickness, anagen and telogen ration, and LC3-II expression in mice, suggesting that ICP5249 promotes hair growth by modulating autophagy, with AMPKα playing a regulatory role in this process. Taken together, we demonstrate that ICP5249 has the potential as an ingredient for improving hair growth.
自噬对于调节毛发生长至关重要。因此，我们开发了自噬激活剂 ICP5249（五钠四羧基甲基棕榈酰二肽），并研究了其在毛发生长中的潜在作用。我们使用人真皮乳头细胞（hDPCs）培养模型、人毛囊（hHFs）器官培养模型和休止期小鼠模型评估了其对毛发生长的影响。ICP5249 增加了 hDPCs 的增殖和碱性磷酸酶（ALP）表达。它还增加了微管相关蛋白（MAP）轻链 3-II（LC3-II）表达以及 hDPCs 中的 AMP 激活蛋白激酶α（AMPKα）和非典型蛋白激酶 1（ULK1）磷酸化。ICP5249 延长了 hHFs 的长度，并增加了 LC3-II 在所有手稿中的表达。一致地，ICP5249 还显著增加了休止期小鼠的毛发生长面积、真皮厚度和生长期与休止期的比例。此外，它还上调了小鼠背部皮肤的 Ki-67 和 LC3-II 表达以及 AMPKα 磷酸化。为了研究 AMPK 是否调节 ICP5249 诱导的毛发生长，在用 AMPK 抑制剂化合物 C 处理后，评估了化合物的活性。在用 AMPK 抑制剂化合物 C 预处理后，评估了 ICP5249 对毛发生长的影响。结果表明，化合物 C 抑制了 ICP5249 介导的 hDPCs 增殖和诱导毛发生长的活性。此外，化合物 C 抑制了 ICP5249 介导的小鼠毛发生长面积、真皮厚度、生长期与休止期的比例和 LC3-II 的表达，表明 ICP5249 通过调节自噬促进毛发生长，AMPKα 在这个过程中发挥调节作用。总之，我们证明了 ICP5249 具有作为改善毛发生长的成分的潜力。
