Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea.
Int J Mol Sci. 2022 Aug 11;23(16):8959. doi: 10.3390/ijms23168959.
Dermal papilla cells (DPCs) are growth factor reservoirs that are specialized for hair morphogenesis and regeneration. Due to their essential role in hair growth, DPCs are commonly used as an in vitro model to investigate the effects of hair growth-regulating compounds and their molecular mechanisms of action. Cyclic adenosine monophosphate (cAMP), an intracellular second messenger, is currently employed as a growth-promoting target molecule. In a pilot test, we found that α-phellandrene, a naturally occurring phytochemical, increased cAMP levels in DPCs. Therefore, we sought to determine whether α-phellandrene increases growth factors and proliferation in human DPCs and to identify the underlying mechanisms. We demonstrated that α-phellandrene promotes cell proliferation concentration-dependently. In addition, it increases the cAMP downstream effectors, such as protein kinase A catalytic subunit (PKA Cα) and phosphorylated cAMP-responsive element-binding protein (CREB). Also, among the CREB-dependent growth factor candidates, we identified that α-phellandrene selectively upregulated vascular endothelial growth factor (VEGF) mRNA expression in DPCs. Notably, the beneficial effects of α-phellandrene were nullified by a cAMP inhibitor. This study demonstrated the cAMP-mediated growth effects in DPCs and the therapeutic potential of α-phellandrene for preventing hair loss.
真皮乳头细胞（DPC）是毛发生长和再生的专门生长因子库。由于其在头发生长中的重要作用，DPC 通常被用作体外模型，以研究毛发生长调节化合物及其作用机制。环磷酸腺苷（cAMP）作为细胞内第二信使，目前被用作促进生长的靶分子。在一项初步测试中，我们发现，一种天然存在的植物化学物质α-水芹烯可增加 DPC 中的 cAMP 水平。因此，我们试图确定α-水芹烯是否能增加人真皮乳头细胞中的生长因子和增殖，并确定其潜在的机制。我们证明α-水芹烯能浓度依赖性地促进细胞增殖。此外，它还增加了 cAMP 的下游效应物，如蛋白激酶 A 催化亚基（PKA Cα）和磷酸化 cAMP 反应元件结合蛋白（CREB）。此外，在 CREB 依赖性生长因子候选物中，我们发现α-水芹烯选择性地上调 DPC 中血管内皮生长因子（VEGF）mRNA 的表达。值得注意的是，cAMP 抑制剂可使α-水芹烯的有益作用失效。本研究证明了 cAMP 介导的 DPC 生长效应，以及α-水芹烯在预防脱发方面的治疗潜力。
