Atopic dermatitis (AD) is characterized by chronic itching and significant loss of skin barrier function. Decreased filaggrin levels have been observed in several patients with AD and are thought to be responsible for impaired barrier function. Caspase-14 is an important factor in maintaining skin barrier function and is involved in the production of natural moisturizing factors by degrading filaggrin. We have been conducting research on Chaenomeles sinensis extract (CSE) and confirmed its anti-aging effects. In this study, we investigated the effects of CSE on caspase-14 expression. CSE-induced changes in gene expression were confirmed in human keratinocytes using DNA microarray and quantitative polymerase chain reaction (qPCR), and the expression of caspase-14 increased. This was confirmed at the protein level using western blotting. Furthermore, CSE increased the expression of kallikrein (KLK) 5 and KLK7, which are involved in skin barrier function, as well as caspase-14. In the investigation of the activation of these factors, CSE promoted activation of caspase-14, KLK5, and KLK7. Moreover, procyanidin B2, gallocatechin gallate, and quercetin were identified using HPLC as CSE components, confirming the strong promotion of caspase-14 activity by quercetin. These results suggest that CSE effectively improves skin barrier function by promoting the expression and activation of caspase-14.
References
[1]
Palmer, C.N.A., Irvine, A.D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S.P., et al. (2006) Common Loss-of-Function Variants of the Epidermal Barrier Protein Filaggrin Are a Major Predisposing Factor for Atopic Dermatitis. Nature Genetics, 38, 441-446. https://doi.org/10.1038/ng1767
[2]
Rodríguez, E., Baurecht, H., Herberich, E., Wagenpfeil, S., Brown, S.J., Cordell, H.J., et al. (2009) Meta-Analysis of Filaggrin Polymorphisms in Eczema and Asthma: Robust Risk Factors in Atopic Disease. Journal of Allergy and Clinical Immunology, 123, 1361-1370.e7. https://doi.org/10.1016/j.jaci.2009.03.036
[3]
Thyssen, J.P. and Kezic, S. (2014) Causes of Epidermal Filaggrin Reduction and Their Role in the Pathogenesis of Atopic Dermatitis. Journal of Allergy and Clinical Immunology, 134, 792-799. https://doi.org/10.1016/j.jaci.2014.06.014
[4]
Yang, G., Seok, J.K., Kang, H.C., Cho, Y., Lee, H.S. and Lee, J.Y. (2020) Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis. International Journal of Molecular Sciences, 21, Article 2867. https://doi.org/10.3390/ijms21082867
[5]
Sakabe, J., Yamamoto, M., Hirakawa, S., Motoyama, A., Ohta, I., Tatsuno, K., et al. (2013) Kallikrein-Related Peptidase 5 Functions in Proteolytic Processing of Profilaggrin in Cultured Human Keratinocytes. Journal of Biological Chemistry, 288, 17179-17189. https://doi.org/10.1074/jbc.m113.476820
[6]
Matsui, T., Miyamoto, K., Kubo, A., Kawasaki, H., Ebihara, T., Hata, K., et al. (2011) Saspase Regulates Stratum Corneum Hydration through Profilaggrin-to-Filaggrin Processing. EMBO Molecular Medicine, 3, 320-333. https://doi.org/10.1002/emmm.201100140
[7]
Hoste, E., Kemperman, P., Devos, M., Denecker, G., Kezic, S., Yau, N., et al. (2011) Caspase-14 Is Required for Filaggrin Degradation to Natural Moisturizing Factors in the Skin. Journal of Investigative Dermatology, 131, 2233-2241. https://doi.org/10.1038/jid.2011.153
[8]
Kamata, Y., Taniguchi, A., Yamamoto, M., Nomura, J., Ishihara, K., Takahara, H., et al. (2009) Neutral Cysteine Protease Bleomycin Hydrolase Is Essential for the Breakdown of Deiminated Filaggrin into Amino Acids. Journal of Biological Chemistry, 284, 12829-12836. https://doi.org/10.1074/jbc.m807908200
[9]
Denecker, G., Hoste, E., Gilbert, B., Hochepied, T., Ovaere, P., Lippens, S., et al. (2007) Caspase-14 Protects against Epidermal UVB Photodamage and Water Loss. Nature Cell Biology, 9, 666-674. https://doi.org/10.1038/ncb1597
[10]
Itoh, S., Yamaguchi, M., Shigeyama, K. and Sakaguchi, I. (2019) The Anti-Aging Potential of Extracts from Chaenomeles Sinensis. Cosmetics, 6, Article 21. https://doi.org/10.3390/cosmetics6010021
[11]
Hamauzu, Y., Inno, T., Kume, C., Irie, M. and Hiramatsu, K. (2006) Antioxidant and Antiulcerative Properties of Phenolics from Chinese Quince, Quince, and Apple Fruits. Journal of Agricultural and Food Chemistry, 54, 765-772. https://doi.org/10.1021/jf052236y
[12]
Kostecka-Gugała, A. (2024) Quinces (Cydonia oblonga, Chaenomeles Sp., and Pseudocydonia sinensis) as Medicinal Fruits of the Rosaceae Family: Current State of Knowledge on Properties and Use. Antioxidants, 13, Article 71. https://doi.org/10.3390/antiox13010071
[13]
Hamauzu, Y., Yasui, H., Inno, T., Kume, C. and Omanyuda, M. (2005) Phenolic Profile, Antioxidant Property, and Anti-Influenza Viral Activity of Chinese Quince (Pseudocydonia sinensis schneid.), Quince (Cydonia oblonga mill.), and Apple (Malus domestica mill.) Fruits. Journal of Agricultural and Food Chemistry, 53, 928-934. https://doi.org/10.1021/jf0494635
[14]
Oku, H., Ueda, Y. and Ishiguro, K. (2003) Antipruritic Effects of the Fruits of Chaenomeles Sinensis. Biological and Pharmaceutical Bulletin, 26, 1031-1034. https://doi.org/10.1248/bpb.26.1031
[15]
Miao, J., Zhao, C., Li, X., Chen, X., Mao, X., Huang, H., et al. (2016) Chemical Composition and Bioactivities of Two Common Chaenomeles Fruits in China: Chaenomeles speciosa and Chaenomeles sinensis. Journal of Food Science, 81, H2049-H2058. https://doi.org/10.1111/1750-3841.13377
[16]
Yang, G., Fen, W., Xiao, W. and Sun, H. (2009) Study on Determination of Pentacyclic Triterpenoids in Chaenomeles by HPLC-ELSD. Journal of Chromatographic Science, 47, 718-722. https://doi.org/10.1093/chromsci/47.8.718
[17]
Du, H., Wu, J., Li, H., Zhong, P., Xu, Y., Li, C., et al. (2013) Polyphenols and Triterpenes from Chaenomeles Fruits: Chemical Analysis and Antioxidant Activities Assessment. Food Chemistry, 141, 4260-4268. https://doi.org/10.1016/j.foodchem.2013.06.109
[18]
Kim, E., Hwang, K., Lee, J., Han, S.Y., Kim, E., Park, J., et al. (2018) Skin Protective Effect of Epigallocatechin Gallate. International Journal of Molecular Sciences, 19, Article 173. https://doi.org/10.3390/ijms19010173
[19]
Yamamoto-Tanaka, M., Makino, T., Motoyama, A., Miyai, M., Tsuboi, R. and Hibino, T. (2014) Multiple Pathways Are Involved in DNA Degradation during Keratinocyte Terminal Differentiation. Cell Death & Disease, 5, e1181-e1181. https://doi.org/10.1038/cddis.2014.145
[20]
Yamamoto, M., Miyai, M., Matsumoto, Y., Tsuboi, R. and Hibino, T. (2012) Kallikrein-Related Peptidase-7 Regulates Caspase-14 Maturation during Keratinocyte Terminal Differentiation by Generating an Intermediate Form. Journal of Biological Chemistry, 287, 32825-32834. https://doi.org/10.1074/jbc.m112.357467
[21]
Nauroy, P. and Nyström, A. (2020) Kallikreins: Essential Epidermal Messengers for Regulation of the Skin Microenvironment during Homeostasis, Repair and Disease. Matrix Biology Plus, 6, Article ID: 100019. https://doi.org/10.1016/j.mbplus.2019.100019
[22]
Murakami, H., Okamura, K., Aoki, S., Sakagami, R. and Yamazaki, J. (2013) Association of Caspase-14 and Filaggrin Expression with Keratinization of the Oral Mucosa and Reconstruction Culture Rat Models. Journal of Periodontal Research, 49, 703-710. https://doi.org/10.1111/jre.12152
[23]
Beken, B., Serttas, R., Yazicioglu, M., Turkekul, K. and Erdogan, S. (2020) Quercetin Improves Inflammation, Oxidative Stress, and Impaired Wound Healing in Atopic Dermatitis Model of Human Keratinocytes. Pediatric Allergy, Immunology, and Pulmonology, 33, 69-79. https://doi.org/10.1089/ped.2019.1137