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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Life Science / Faculty of Advanced Life Science >
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Konjac Ceramide (kCer)-Mediated Signal Transduction of the Sema3A Pathway Promotes HaCaT Keratinocyte Differentiation
| Title: | Konjac Ceramide (kCer)-Mediated Signal Transduction of the Sema3A Pathway Promotes HaCaT Keratinocyte Differentiation |
| Authors: | Usuki, Seigo Browse this author | | Tamura, Noriko Browse this author | | Tamura, Tomohiro Browse this author | | Yuyama, Kohei Browse this author →KAKEN DB | | Mikami, Daisuke Browse this author | | Mukai, Katsuyuki Browse this author | | Igarashi, Yasuyuki Browse this author →KAKEN DB |
| Keywords: | ceramide | | konjac | | keratinocyte | | differentiation | | neuropilin1 |
| Issue Date: | Jan-2022 |
| Publisher: | MDPI |
| Journal Title: | Biology (Basel) |
| Volume: | 11 |
| Issue: | 1 |
| Start Page: | 121 |
| Publisher DOI: | 10.3390/biology11010121 |
| Abstract: | 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/85061 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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