Human placental extract exerts hair growth-promoting effects through the GSK-3β signaling pathway in human dermal papilla cells

Kwon,Tae‑Rin; Oh,Chang  Taek; Choi,Eun  Ja; Park,Hye  Min; Han,Hae  Jung; Ji,Hyi  Jeong; Kim,Beom  Joon

doi:10.3892/ijmm.2015.2316

Human placental extract exerts hair growth-promoting effects through the GSK-3β signaling pathway in human dermal papilla cells

Authors:
- Tae‑Rin Kwon
- Chang Taek Oh
- Eun Ja Choi
- Hye Min Park
- Hae Jung Han
- Hyi Jeong Ji
- Beom Joon Kim
View Affiliations

Affiliations: Major in Biomedical Science, Department of Medicine, Graduate School, Chung‑Ang University, Seoul 156‑755, Republic of Korea, Green Cross Corporation, Giheung‑gu, Yongin-si, Gyeonggi-do 446-770, Republic of Korea
Published online on: August 19, 2015 https://doi.org/10.3892/ijmm.2015.2316
Pages: 1088-1096

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Human placental extract (HPE) is widely used in Korea to relieve fatigue. However, its effects on human dermal papilla cells (hDPCs) remain unknown. In the present study, in an effort to develop novel therapies to promote hair growth, we screened HPE. We demonstrate that HPE has hair growth‑promoting activities and induces β‑catenin expression through the inhibition of glycogen synthase kinase‑3β (GSK‑3β) by phosphorylation in hDPCs. Treatment with HPE significantly increased the viability of the hDPCs in a concentration‑dependent manner, as shown by bromodeoxyuridine (BrdU) assay. HPE also significantly increased the alkaline phosphatase (ALP) expression levels. The increased β‑catenin levels and the inhibition of GSK‑3β (Ser9) by phosphorylation suggested that HPE promoted the hair-inductive capacity of hDPCs. We compared the effects of treatment with HPE alone and treatment with HPE in conjunction with minoxidil (MXD). We found that HPE plus MXD effectively inhibited GSK‑3β by phosphorylation (Ser9) in the hDPCs. Moreover, we demonstrated that HPE was effective in inducing root hair elongation in rat vibrissa hair follicles, and that treatment with HPE led to a delay in catagen progression. Overall, our findings suggest that HPE promotes hair growth and may thus provide the basis of a novel therapeutic strategy for the clinical treatment of hair loss.

View Figures

View References

1	Paus R and Cotsarelis G: The biology of hair follicles. N Engl J Med. 341:491–497. 1999. View Article : Google Scholar : PubMed/NCBI
2	Hardy MH: The secret life of the hair follicle. Trends Genet. 8:55–61. 1992. View Article : Google Scholar : PubMed/NCBI
3	Stenn KS and Paus R: Controls of hair follicle cycling. Physiol Rev. 81:449–494. 2001.PubMed/NCBI
4	Nair B and Elmore AR; Cosmetic Ingredient Review Expert panel: Final report on the safety assessment of human placental protein, hydrolyzed human placental protein, human placental enzymes, human placental lipids, human umbilical extract, placental protein, hydrolyzed placental protein, placental enzymes, placental lipids, and umbilical extract. Int J Toxicol. 21(Suppl 1): 81–91. 2002. View Article : Google Scholar
5	Shibasaki T, Odagiri E, Shizume K and Ling N: Corticotropin-releasing factor-like activity in human placental extracts. J Clin Endocrinol Metab. 55:384–386. 1982. View Article : Google Scholar : PubMed/NCBI
6	Jung J, Lee HJ, Lee JM, Na KH, Hwang SG and Kim GJ: Placenta extract promote liver regeneration in CCl4-injured liver rat model. Int Immunopharmacol. 11:976–984. 2011. View Article : Google Scholar : PubMed/NCBI
7	Liu KX, Kato Y, Kaku T and Sugiyama Y: Human placental extract stimulates liver regeneration in rats. Biol Pharm Bull. 21:44–49. 1998. View Article : Google Scholar : PubMed/NCBI
8	Sur TK, Biswas TK, Ali L and Mukherjee B: Anti-inflammatory and anti-platelet aggregation activity of human placental extract. Acta Pharmacol Sin. 24:187–192. 2003.PubMed/NCBI
9	Rosen T, Krikun G, Ma Y, Wang EY, Lockwood CJ and Guller S: Chronic antagonism of nuclear factor-kappaB activity in cytoblasts by dexamethasone: a potential mechanismfor antiinflammatory action of glucocorticoids in human placenta. J Clin Endocrinol Metab. 83:3647–3652. 1998.PubMed/NCBI
10	Topical minoxidil approved by FDA. Clin Pharm. 7:8588621988.
11	Rossi A, Cantisani C, Melis L, Iorio A, Scali E and Calvieri S: Minoxidil use in dermatology, side effects and recent patents. Recent Pat Inflamm Allergy Drug Discov. 6:130–136. 2012. View Article : Google Scholar : PubMed/NCBI
12	Morokuma Y, Yamazaki M, Maeda T, Yoshino I, Ishizuka M, Tanaka T, Ito Y and Tsuboi R: Hair growth stimulatory effect by a combination of 5-aminolevulinic acid and iron ion. Int J Dermatol. 47:1298–1303. 2008. View Article : Google Scholar
13	Rastegar H, Ahmadi Ashtiani H, Aghaei M, Ehsani A and Barikbin B: Combination of herbal extracts and platelet-rich plasma induced dermal papilla cell proliferation: involvement of ERK and Akt pathways. J Cosmet Dermatol. 12:116–122. 2013. View Article : Google Scholar : PubMed/NCBI
14	Loing E, Lachance R, Ollier V and Hocquaux M: A new strategy to modulate alopecia using a combination of two specific and unique ingredients. J Cosmet Sci. 64:45–58. 2013.PubMed/NCBI
15	Chu EY, Hens J, Andl T, Kairo A, Yamaguchi TP, Brisken C, Glick A, Wysolmerski JJ and Millar SE: Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development. 131:4819–4829. 2004. View Article : Google Scholar : PubMed/NCBI
16	Soma T, Fujiwara S, Shirakata Y, Hashimoto K and Kishimoto J: Hair-inducing ability of human dermal papilla cells cultured under Wnt/β-catenin signalling activation. Exp Dermatol. 21:307–309. 2012. View Article : Google Scholar : PubMed/NCBI
17	Clevers H and Nusse R: Wnt/β-catenin signaling and disease. Cell. 149:1192–1205. 2012. View Article : Google Scholar : PubMed/NCBI
18	Woodgett JR: Judging a protein by more than its name: GSK-3. Sci STKE. 2001:re122001.PubMed/NCBI
19	Li L, Yuan H, Weaver CD, Mao J, Farr GH III, Sussman DJ, Jonkers J, Kimelman D and Wu D: Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1. EMBO J. 18:4233–4240. 1999. View Article : Google Scholar : PubMed/NCBI
20	Jo SJ, Choi SJ, Yoon SY, Lee JY, Park WS, Park PJ, Kim KH, Eun HC and Kwon O: Valproic acid promotes human hair growth in in vitro culture model. J Dermatol Sci. 72:16–24. 2013. View Article : Google Scholar : PubMed/NCBI
21	Philpott MP and Kealey T: Cyclical changes in rat vibrissa follicles maintained In vitro. J Invest Dermatol. 115:1152–1155. 2000. View Article : Google Scholar : PubMed/NCBI
22	Handjiski BK, Eichmüller S, Hofmann U, Czarnetzki BM and Paus R: Alkaline phosphatase activity and localization during the murine hair cycle. Br J Dermatol. 131:303–310. 1994. View Article : Google Scholar : PubMed/NCBI
23	Kwack MH, Kang BM, Kim MK, Kim JC and Sung YK: Minoxidil activates β-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect. J Dermatol Sci. 62:154–159. 2011. View Article : Google Scholar : PubMed/NCBI
24	Hwang KA, Hwang YL, Lee MH, Kim NR, Roh SS, Lee Y, Kim CD, Lee JH and Choi KC: Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles. Int J Mol Med. 29:195–201. 2012.
25	Yoon SY, Yoon JS, Jo SJ, Shin CY, Shin JY, Kim JI, Kwon O and Kim KH: A role of placental growth factor in hair growth. J Dermatol Sci. 74:125–134. 2014. View Article : Google Scholar : PubMed/NCBI
26	Abdullah F and Rashid RM: Alopecia: Botanical approaches in review. J Drugs Dermatol. 9:537–541. 2010.PubMed/NCBI
27	Frankel S: Study of the food and drug administration files on Propecia: dosages, side effects, and recommendations. Arch Dermatol. 135:257–258. 1999. View Article : Google Scholar : PubMed/NCBI
28	Irwig MS and Kolukula S: Persistent sexual side effects of finas-teride for male pattern hair loss. J Sex Med. 8:1747–1753. 2011. View Article : Google Scholar : PubMed/NCBI
29	Trüeb RM: Chemotherapy-induced hair loss. Skin Therapy Lett. 15:5–7. 2010.PubMed/NCBI
30	Lourith N and Kanlayavattanakul M: Hair loss and herbs for treatment. J Cosmet Dermatol. 12:210–222. 2013. View Article : Google Scholar : PubMed/NCBI
31	Rahmani M, Wong BW, Ang L, Cheung CC, Carthy JM, Walinski H and McManus BM: Versican: signaling to transcriptional control pathways. Can J Physiol Pharmacol. 84:77–92. 2006. View Article : Google Scholar : PubMed/NCBI
32	du Cros DL, LeBaron RG and Couchman JR: Association of versican with dermal matrices and its potential role in hair follicle development and cycling. J Invest Dermatol. 105:426–431. 1995. View Article : Google Scholar : PubMed/NCBI
33	Wight TN: Arterial remodeling in vascular disease: a key role for hyaluronan and versican. Front Biosci. 13:4933–4937. 2008. View Article : Google Scholar : PubMed/NCBI
34	Yang Y, Li Y, Wang Y, Wu J, Yang G, Yang T, Gao Y and Lu Y: Versican gene: regulation by the β-catenin signaling pathway plays a significant role in dermal papilla cell aggregative growth. J Dermatol Sci. 68:157–163. 2012. View Article : Google Scholar : PubMed/NCBI
35	Lee SH, Yoon J, Shin SH, Zahoor M, Kim HJ, Park PJ, Park WS, Min S, Kim HY and Choi KY: Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells. PLoS One. 7:e341522012. View Article : Google Scholar : PubMed/NCBI
36	Hibino T and Nishiyama T: Role of TGF-beta2 in the human hair cycle. J Dermatol Sci. 35:9–18. 2004. View Article : Google Scholar : PubMed/NCBI