Sophora japonica extracts accelerates keratinocyte differentiation through miR-181a
Tóm tắt
The Sophora japonica extracts contain flavonol triglycoside, isoflavonol, coumarone chromone, saponin, triterpene glucoside, phospholipids, alkaloids, amino acids, polysaccharides, and fatty acids. These components have physiological effects such as anti-infertility and anti-cancer activities. This study investigated the regulation of keratinocyte differentiation upon treatment with the S. japonica extracts in keratinocyte and the molecular cell biological mechanism involved. To determine whether the S. japonica extracts or troxerutin, which is its main component, regulates keratinocyte differentiation, quantitative real-time polymerase chain reaction (qRT-PCR) was performed on keratinocyte differentiation markers such as keratin 1 (K1), keratin 10 (K10), involucrin, and filaggrin after treatment with the S. japonica extracts. miR-181a knockdown confirmed that keratinocyte differentiation was regulated by increased miR-181a expression upon treatment with the S. japonica extracts or troxerutin. The expression of keratinocyte differentiation markers such as K1, K10, involucrin, and filaggrin increased upon treatment with the S. japonica extracts and troxerutin. Furthermore, miR-181a expression, which is known to increase during keratinocyte differentiation, increased upon treatment with the S. japonica extracts and troxerutin. When miR-181a was knocked down, the increased expression of keratinocyte differentiation markers upon treatment with the S. japonica extracts and troxerutin decreased again. Finally, it was confirmed that miR-181a directly regulated and reduced the expression of Notch2, which reduces keratinocyte differentiation, and that the decrease in Notch2 expression by miR-181a regulated keratinocyte differentiation. These results suggest that the S. japonica extracts or troxerutin accelerates keratinocyte differentiation through miR-181a. This accelerated keratinocyte differentiation was confirmed to have resulted from the regulation of Notch2 expression by miR-181a. The results of this study provide an opportunity to confirm the molecular cell biological mechanism of S. japonica extracts or troxerutin on skin keratinization, and we expected that this study contribute to develop a moisturizing cosmetic material that can strengthen the skin barrier through regulating keratinocyte differentiation.
Tài liệu tham khảo
Bollag WB, Ducote J, Harmon CS. Effects of the selective protein kinase C inhibitor, Ro 31-7549, on the proliferation of cultured mouse epidermal keratinocytes. J Invest Dermatol. 1993;100:240–6.
Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005;6(4):328–40.
Chuong CM, Nickoloff BJ, Elias PM, Goldsmith LA, Macher E, Maderson PA, Sundberg JP, Tagami H, Plonka PM, Thestrup-Pederson K, Bernard BA, Schroder JM, Dotto P, Chang CM, Williams ML, Feingold KR, King LE, Kligman AM, Rees JL, Christophers E. What is the ‘true’ function of skin? Exp Dermatol. 2002;11:159–87.
Dlugosz AA, Yuspa SH. Coordinate changes in gene expression which mark the spinous to granular cell transition in epidermis are regulated by protein kinase C. J Cell Biol. 1993;120:217–25.
Eckert RL, Efimova T, Dashti SR, Balasubramanian S, Deucher A, Crish JF, Sturniolo M, Bone F. Keratinocyte survival, differentiation, and death: many roads lead to mitogen-activated protein kinase. J Investig Dermatol Symp Proc. 2002;7:36–40.
Efimova T, Broome AM, Eckert RL. A regulatory role for p38 delta MAPK in keratinocyte differentiation. Evidence for p38 delta-ERK1/2 complex formation. J Biol Chem. 2003;278:34277–85.
Fuchs E. Epidermal differentiation and keratin gene expression. J Cell Sci. 1993;17:197–208.
Grupp C, John H, Hemprich U, Singer A, Munzel U, Muller GA. Identification of nucleated cells in urine using lectin staining. Am J Kidney Dis. 2001;37:84–93.
Hennings H, Michael D, Cheng C, Steinert P, Holbrook K, Yuspa SH. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell. 1980;19:245–54.
Hildebrand J, Rütze M, Walz N, Gallinat S, Wenck H, Deppert W, Grundhoff A, Knott A. A comprehensive analysis of microRNA expression during human keratinocyte differentiation in vitro and in vivo. J Invest Dermatol. 2011;131(1):20–9.
Ishida-Yamamoto A, Iizuka H. Structural organization of cornified cell envelopes and alterations in inherited skin disorders. Exp Dermatol. 1998;7(1):1–10.
Jang SI, Steinert PM. Loricrin expression in cultured human keratinocytes is controlled by a complex interplay between transcription factors of the Sp1, CREB, AP1, and AP2 families. J Biol Chem. 2002;277:42268–79.
Kalinin AE, Kajava AV, Steinert PM. Epithelial barrier function: assembly and structural features of the cornified cell envelope. BioEssays. 2002;24:789–800.
Lee JH, Jang SI, Yang JM, Markova NG, Steinert PM. The proximal promoter of the human transglutaminase 3 gene. Stratified squamous epithelial-specific expression in cultured cells is mediated by binding of Sp1 and ets transcription factors to a proximal promoter element. J Biol Chem. 1996;271:4561–8.
Leung AK, Hon KL, Robson WL. Atopic dermatitis. Adv Pediatr Infect Dis. 2007;54:241–73.
Lo YH, Lin RD, Lin YP, Liu YL, Lee MH. Active constituents from Sophora japonica exhibiting cellular tyrosinase inhibition in human epidermal melanocytes. J Ethnopharmacol. 2009;124(3):625–9.
Ma L, Lou FC. The anticancer activity in vitro of constituents from fruits of Sophora japonica. Chinese J of Nat Med. 2006;4:151–3.
Matsui MS, Chew SL, DeLeo VA. Protein kinase C in normal human epidermal keratinocytes during proliferation and calcium-induced differentiation. J Invest Dermatol. 1992;99:565–71.
Menon GK, Grayson S, Elias P. Ionic calcium reservoirs in mammalian epidermis: ultrastructural localization by ion-capture cytochemistry. J Invest Dermatol. 1985;84:508–12.
Nakamura Y, Kawachi Y, Xu X, Sakurai H, Ishii Y, Takahashi T, Otsuka F. The combination of ubiquitous transcription factors AP-1 and Sp1 directs keratinocytespecific and differentiation-specific gene expression in vitro. Exp Dermatol. 2007;16:143–50.
O’Driscoll KR, Madden PV, Christiansen KM, Viage A, Slaga TJ, Fabbro D, Powell CT, Weinstein IB. Overexpression of protein kinase C beta I in a murine keratinocyte cell line produces effects on cellular growth, morphology and differentiation. Cancer Lett. 1994;83:249–59.
Rice RH, Green H. The cornified envelope of terminally differentiated human epidermal keratinocytes consists of crosslinked protein. Cell. 1977;11:417–22.
Steinert PM, Marekov LN. The proteins elafin, filaggrin, keratin intermediate filaments, loricrin, and small prolinerich proteins 1 and 2 are isodipeptide cross-linked components of the human epidermal cornified cell envelope. J Biol Chem. 1995;270:17702–11.
Tsuchisaka A, Furumura M, Hashimoto T. Cytokine regulation during epidermal differentiation and barrier formation. J Invest Dermatol. 2014;134(5):1194–6.
Wang JH, Wang YL, Lou FC. Acacia trees the chemical constituents of the seeds. J China Pharma Univ. 2001;32:471.
Yuspa SH, Kilkenny AE, Steinert PM, Roop DR. Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro. J Cell Biol. 1989;109:1207–17.
Zhao ZZ. An Illustrated Chinese Materia Medica in Hong Kong. School of Chinese Medicine. Hong Kong: Hong Kong Baptist University 2004.