Choi Nahyun, Sung Jong-Hyuk
College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea.
STEMORE Co. Ltd., Incheon 21984, Republic of Korea.
Biomol Ther (Seoul). 2019 Jul 1;27(4):404-413. doi: 10.4062/biomolther.2018.195.
Udenafil, which is a PDE inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafiltreated ASCs accelerated telogen-to-anagen transition . We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and NFκB. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or NFκB knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and NFκB pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.
伐地那非是一种磷酸二酯酶（PDE）抑制剂，用于治疗勃起功能障碍。然而，尚不清楚伐地那非是否通过刺激脂肪来源干细胞（ASC）来促进毛发生长。在本研究中，我们调查了伐地那非是否刺激ASC，以及ASC分泌的生长因子增加是否有助于毛发生长。我们发现皮下注射经伐地那非处理的ASC可加速休止期到生长期的转变。我们还观察到伐地那非可诱导ASC的增殖、迁移和管腔形成。它还增加了ASC分泌的生长因子，如白细胞介素-4（IL-4）和IL12B，以及ERK1/2和NFκB的磷酸化。此外，ERK抑制剂或NFκB敲低可减弱IL-4和IL12B mRNA水平的同时上调。应用IL-4或IL12B可增强小鼠的生长期诱导，并增加器官培养中的毛囊长度。结果表明，伐地那非可刺激ASC的运动能力，并增加旁分泌生长因子，包括细胞因子信号传导。伐地那非刺激ASC分泌细胞因子可能通过ERK和NFκB途径促进毛发生长。因此，伐地那非可作为一种用于毛发生长的ASC预处理剂。
