title: Platelets Regulate the Migration of Keratinocytes via Podoplanin/CLEC-2 Signaling during Cutaneous Wound Healing in Mice.
abstract: Podoplanin is an endogenous ligand for C-type lectin-like receptor 2 (CLEC-2), which is expressed on platelets. Recent evidence indicates that this specific marker of lymphatic endothelial cells is also expressed by keratinocytes at the edge of wounds. However, whether podoplanin or platelets play a role in keratinocyte activity during wound healing remains unknown. We evaluated the effect of podoplanin expression levels on keratinocyte motility using cultured primary normal human epidermal keratinocytes (NHEKs). Down-regulation of podoplanin in NHEKs via transfection with podoplanin siRNA inhibited their migration, indicating that podoplanin plays a mandatory role in this process. In addition, down-regulation of podoplanin was correlated with up-regulation of E-cadherin, suggesting that podoplanin-mediated stimulation of keratinocyte migration is associated with a loss of E-cadherin. Both the addition of platelets and treatment with CLEC-2 inhibited the migration of NHEKs. The down-regulation of RhoA activity and the up-regulation of E-cadherin in keratinocytes were also induced by CLEC-2. In conclusion, these results suggest that podoplanin/CLEC-2 signaling regulates keratinocyte migration via modulating E-cadherin expression through RhoA signaling. Altering the regulation of keratinocyte migration by podoplanin might be a novel therapeutic approach to improve wound healing.
authors.affiliation: Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: jasai@koto.kpu-m.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Asai
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirakawa
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sakabe
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.affiliation: Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Wada
authors.affiliation: Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Takenaka
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
authors.affiliation: Department of Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tetsumei
authors.initials: T
authors.lastname: Urano
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Kofu, Japan.
authors.forename: Katsue
authors.initials: K
authors.lastname: Suzuki-Inoue
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
authors.affiliation: Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Norito
authors.initials: N
authors.lastname: Katoh
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004817:Epidermis / Q000293:injuries / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014945:Wound Healing / Q000502:physiology*; D000098853:Podoplanin
chemical_list: D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C529518:CLEC-2 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin