Browse > Article
http://dx.doi.org/10.15230/SCSK.2018.44.1.95

Betaine Induces Epidermal Differentiation by Enhancement of Autophagy through an mTOR-independent Pathway  

Choi, Seon-Guk (R&D Center, LG Household & Healthcare Ltd.)
Kim, Mi-Sun (R&D Center, LG Household & Healthcare Ltd.)
Kim, Jin-Hyun (R&D Center, LG Household & Healthcare Ltd.)
Park, Sun Gyoo (R&D Center, LG Household & Healthcare Ltd.)
Lee, Cheon Koo (R&D Center, LG Household & Healthcare Ltd.)
Kang, Nae-Gyu (R&D Center, LG Household & Healthcare Ltd.)
Publication Information
Journal of the Society of Cosmetic Scientists of Korea / v.44, no.1, 2018 , pp. 95-101 More about this Journal
Abstract
The epidermis which is stratified by epithelial tissue renewal based on keratinocyte differentiation protects the organism from various environmental insults by forming a physical barrier. Autophagy is a mechanism which mediates lysosomal delivery and degradation of protein aggregates, damaged organelles and intracellular microorganisms. Recent reports have shown that autophagy has critical roles for proper terminal differentiation to stratum corneum via removing metabolic organelles and nuclei. However, whether increasing autophagy can activate epidermal differentiation is unknown. Here, we screened a library of natural single compounds and discovered that betaine specifically increased the LC3 positive cytosolic punctate vesicles and LC3-I to LC3-II conversion in HaCaT human keratinocyte cell line, indicating increased autophagy flux. mTOR pathway, which negatively regulates autophagy, was not affected by betaine treatment, suggesting betaine-induced autophagy through an mTOR-independent pathway. Betaine-induced autophagy was also observed in primary human keratinocyte and skin equivalent. Furthermore, epidermal thickness was increased in skin equivalent under betaine treatment. Overall, our finding suggests that betaine as a novel regulator of autophagy may induce epidermal turnover and improve the skin barrier abnormality of the aged epidermis.
Keywords
betaine; autophagy; keratinocyte; mTOR; cosmetics;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Y. Zhao, C. F. Zhang, H. Rossiter, L. Eckhart, U. Konig, S. Karner, M. Mildner, V. N. Bochkov, E. Tschachler, and F. Gruber, Autophagy is induced by UVA and promotes removal of oxidized phospholipids and protein aggregates in epidermal keratinocytes, J. Invest. Dermatol., 133(6), 1629 (2013).   DOI
2 L. Qiang, C. Wu, M. Ming, B. Viollet, and Y. Y. He, Autophagy controls p38 activation to promote cell survival under genotoxic stress, J. Biol. Chem., 288(3), 1603 (2013).   DOI
3 I. Hurbain, M. Romao, P. Sextius, E. Bourreau, C. Marchal, F. Bernerd, C. Duval, and G. Raposo, Melanosome distribution in keratinocytes in different skin types: melanosome clusters are not degradative organelles, J. Invest. Dermatol., 138(3), 647 (2018).   DOI
4 L. M. Griffin, L. Cicchini, and D. Pyeon, Human papillomavirus infection is inhibited by host autophagy in primary human keratinocytes, Virology, 437(1), 12 (2013).   DOI
5 K. H. Kim and M. S. Lee, Autophagy - a key player in cellular and body metabolism, Nat. Rev. Endocrinol., 10(6), 322 (2014).   DOI
6 S. Davidson, B. A. Hopkins, J. Odle, C. Brownie, V. Fellner, and L. W. Whitlow, Supplementing limited methionine diets with rumen-protected methionine, betaine, and choline in early lactation holstein cows, Journal of Dairy Science., 91(4), 1552 (2008).   DOI
7 M. T. Kidd, P. R. Ferket, and J. D. Garlich, Nutritional and osmoregulatory functions of betaine, World's Poultry Science Journal, 53(2), 125 (2007).
8 E. S. Basheva, S. Stoyanov, N. D. Denkov, K. Kasuga, N. Satoh, and K. Tsujii, Foam boosting by amphiphilic molecules in the presence of silicone oil, Langmuir, 17(4), 969 (2001).   DOI
9 N. Mizushima, T. Yoshimorim, and B. Levine, Methods in mammalian autophagy research, Cell, 140(3), 313 (2010).   DOI
10 P. A. Sotiropoulou and C. Blanpain., Development and homeostasis of the skin epidermis, Cold Spring Harb. Perspect. Biol., 4(7), a008383 (2012).   DOI
11 N. D. Magnani, X. M. Muresan, G. Belmonte, F. Cervellati, C. Sticozzi, A. Pecorelli, C. Miracco, T. Marchini, P. Evelson, and G. Valacchi, Skin damage mechanisms related to airborne particulate matter exposure, Toxicol. Sci., 149(1), 227 (2016).   DOI
12 R. R. Wickett and M. O. Visscher, Structure and function of the epidermal barrier, Am. J. Infect. Control., 34(10), S98 (2006).   DOI
13 R. M. Lavker and A. G. Matoltsy, Formation of horny cells: the fate of cell organelles and differentiation products in ruminal epithelium, J. Cell. Biol., 44(3), 501 (1970).   DOI
14 M. Moriyama, H. Moriyama, J. Uda, A. Matsuyama, M. Osawa, and T. Hayakawa, BNIP3 plays crucial roles in the differentiation and maintenance of epidermal keratinocytes, J. Invest. Dermatol., 134(6), 1627 (2014).   DOI
15 K. Khayati, H. Antikainen, E. M. Bonder, G. F. Weber, W. D. Kruger, H. Jakubowski, and R. Dobrowolski, The amino acid metabolite homocysteine activates mTORC1 to inhibit autophagy and form abnormal proteins in human neurons and mice, The FASEB Journal, 31(2), 598 (2017).   DOI
16 Q. Feng, K. Kalari, B. L. Fridley, G. Jenkins, Y. Ji, R. Abo, S. Hebbring, J. Zhang, M. D. Nye, J. S. Leeder, and R. M. Weinshilboum, Betaine-homocysteine methyltransferase: human liver genotype-phenotype correlation, Molecular genetics and metabolism, 102(2), 126 (2011).   DOI
17 E. Aymard, V. Barruche, T. Naves, S. Bordes, B. Closs, M. Verdier, and M. H. Ratinaud, Autophagy in human keratinocytes: an early step of the differentiation?, Exp. Dermatol., 20(3), 263 (2011).   DOI
18 R. M. Lavker, Horny cell formation in the epidermis of Rana pipiens, J. Morphol., 142(4), 365 (1974).   DOI
19 O. Akinduro, K. Sully, A. Patel, D. J. Robinson, A. Chikh, G. McPhail, K. M. Braun, M. P. Philpott, C. A. Harwood, and C. Byrne, Constitutive autophagy and nucleophagy during epidermal differentiation, J. Invest. Dermatol., 136(7), 1460 (2016).   DOI
20 Q. Dong, J. E. Oh, J. K. Yi, R. H. Kim, K. H. Shin, R. Mitsuyasu, N. H. Park, and M. K. Kang, Efavirenz induces autophagy and aberrant differentiation in normal human keratinocytes, Int. J. Mol. Med., 31(6), 1305 (2013).   DOI
21 B. B. Bridgeman, P. Wang, B. Ye, J. C. Pelling, O. V. Volpert, and X. Tong, Inhibition of mTOR by apigenin in UVB-irradiated keratinocytes: A new implication of skin cancer prevention, Cellular signalling, 28(5), 460 (2016).   DOI
22 X. Chen, M. Li, L. Li, S. Xu, D. Huang, M. Ju, J. Huang, K. Chen, and H. Gu, Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway, Sci. Rep., 6, 28423 (2016).   DOI