Biomol Ther  
Udenafil Induces the Hair Growth Effect of Adipose-Derived Stem Cells
Nahyun Choi1,2,* and Jong-Hyuk Sung1,2,*
E-mail: brian99@empal.com (Sung JH), nh147837@gmail.com (Choi N)
Tel: +82-32-749-4506 (Sung JH), +82-32-749-4165 (Choi N)
Received: October 8, 2018; Revised: January 1, 2019; Accepted: February 25, 2019; Published online: April 10, 2019.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Udenafil, which is a PDE5 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 in vivo. 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.
Keywords: Udenafil, Adipose-derived stem cells, IL-4, IL12B, Hair growth


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