title: Collagen XVII participates in keratinocyte adhesion to collagen IV, and in p38MAPK-dependent migration and cell signaling.
abstract: Collagen XVII (COL17) participates in keratinocyte adhesion and possibly migration, as COL17 defects disrupt keratinocyte-basal lamina adhesion and underlie the disease non-Herlitz junctional epidermolysis bullosa. Using small interference RNA (siRNA) to knock down COL17 expression in HaCaT cells, we assessed cell characteristics, including adhesion, migration, and signaling. Control and siRNA-transfected keratinocytes showed no difference in adhesion on plastic dishes after incubation for 8 hours in serum-free keratinocyte-growth medium; however, when grown on collagen IV alone or BD matrigel (containing collagen IV and laminin isoforms), COL17-deficient cells showed significantly reduced adhesion compared with controls (P<0.01), and mitogen-activated protein kinase (MAPK)/ERK kinase (MEK)1/2 and MAPK showed reduced phosphorylation. Furthermore, COL17-deficient HaCaT cells plated on plastic exhibited reduced motility that was p38MAPK-dependent (after addition of the p38MAPK inhibitor SB203580). Together, these results suggest that COL17 has significantly wider signaling roles than were previously thought, including the involvement of COL17 in keratinocyte adhesion to collagen IV, in p38MAPK-dependent cell migration, and multiple cell signaling events pertaining to MEK1/2 phosphorylation.
authors.affiliation: Creative Research Initiative, Hokkaido University, Sapporo, Japan.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Qiao
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shibaki
authors.forename: Heather A
authors.initials: HA
authors.lastname: Long
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Wataru
authors.initials: W
authors.lastname: Nishie
authors.forename: Riichiro
authors.initials: R
authors.lastname: Abe
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: James R
authors.initials: JR
authors.lastname: McMillan
mesh_terms: D001324:Autoantigens / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D024041:Non-Fibrillar Collagens / Q000502:physiology*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024141:Collagen Type IV; D048049:Extracellular Signal-Regulated MAP Kinases; D024041:Non-Fibrillar Collagens; D048051:p38 Mitogen-Activated Protein Kinases; D000097805:Collagen Type XVII