Konjac Ceramide (kCer)-Mediated Signal Transduction of the Sema3A Pathway Promotes HaCaT Keratinocyte Differentiation

Usuki, Seigo; Tamura, Noriko; Tamura, Tomohiro; Yuyama, Kohei; Mikami, Daisuke; Mukai, Katsuyuki; Igarashi, Yasuyuki

Konjac Ceramide (kCer)-Mediated Signal Transduction of the Sema3A Pathway Promotes HaCaT Keratinocyte Differentiation

Usuki, Seigo; Tamura, Noriko; Tamura, Tomohiro et al.

Biology (Basel), 2022, 11(1), 121

Permalink : https://hdl.handle.net/2115/85061

このアイテムのアクセス数:374件（2026-01-15 08:23 集計）

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https://doi.org/10.3390/biology11010121

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アクセス権	metadata only access
URI	https://hdl.handle.net/2115/85061
タイトル	Konjac Ceramide (kCer)-Mediated Signal Transduction of the Sema3A Pathway Promotes HaCaT Keratinocyte Differentiation
著者	Usuki, Seigo ; Tamura, Noriko ; Tamura, Tomohiro ; Yuyama, Kohei ; Mikami, Daisuke ; Mukai, Katsuyuki ; Igarashi, Yasuyuki
著者名 Usuki, Seigo
著者名 Tamura, Noriko
著者名 Tamura, Tomohiro
e-Rad_Researcher 80415546 著者名 Yuyama, Kohei
著者名 Mikami, Daisuke
著者名 Mukai, Katsuyuki
e-Rad_Researcher 70091965 著者名 Igarashi, Yasuyuki
言語	英語
キーワード	ceramide
	konjac
	keratinocyte
	differentiation
	neuropilin1
発行日	2022-01
出版者	MDPI
収録物名	Biology (Basel)
巻(号)	11(1)
ページ	121
抄録	Simple Summary Konjac ceramide (kCer) is a unique molecular species of plant-type ceramide, and is a potential Sema3A-like ligand of Nrp1. kCer suppresses histamine-stimulated cell migration of HaCaT keratinocytes. This effect of kCer is not due to histamine-activated GPCRs, but rather to Sema3A-Nrp1 receptor binding. The present study focused on the ability of kCer to induce cell differentiation, in addition to its anti-migratory effects. We demonstrated that the effects of kCer on cell migration and cell differentiation are perpetuated by a cascade of crosstalk between pathways downstream of Nrp1 and GPCR in HaCaT cells. Histamines suppress epidermal keratinocyte differentiation. Previously, we reported that konjac ceramide (kCer) suppresses histamine-stimulated cell migration of HaCaT keratinocytes. kCer specifically binds to Nrp1 and does not interact with histamine receptors. The signaling mechanism of kCer in HaCaT cells is also controlled by an intracellular signaling cascade activated by the Sema3A-Nrp1 pathway. In the present study, we demonstrated that kCer treatment induced HaCaT keratinocyte differentiation after migration of immature cells. kCer-induced HaCaT cell differentiation was accompanied by some features of keratinocyte differentiation markers. kCer induced activating phosphorylation of p38MAPK and c-Fos, which increased the protein levels of involucrin that was the latter differentiation marker. In addition, we demonstrated that the effects of both kCer and histamines are regulated by an intracellular mechanism of Rac1 activation/RhoA inhibition downstream of the Sema3A/Nrp1 receptor and histamine/GPCR pathways. In summary, the effects of kCer on cell migration and cell differentiation are regulated by cascade crosstalk between downstream Nrp1 and histamine-GPCR pathways in HaCaT cells.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
EISSN	2079-7737
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.3390/biology11010121