title: Alginates induce differentiation and expression of CXCR7 and CXCL12/SDF-1 in human keratinocytes--the role of calcium.
abstract: Alginates from seaweed are used in chronic wound management, though the molecular and cellular effects of various alginate dressings are not well documented. We have developed ultrapure sodium-alginates from Pseudomonas fluorescens with different content and distribution of single guluronic acid (G) residues (0-45% G), and tested their biological activities on human primary keratinocytes (KCs). The alginates inhibited KC migration and induced expression of differentiation markers. The potency of the alginates correlated with the increasing percentage of single G residues. These findings were explained by different binding and release of ionic calcium (Ca++) from the alginates which subsequently triggered differentiation. Ca-free alginates had no effect on KC migration and differentiation, but the chemokine receptor CXCR7 was upregulated. Q-PCR revealed that also CXCL12/SDF-1, one of two known CXCR7-ligands, was induced by the alginates. Both CXCR7 and CXCL12-induction was dependent on the alginate G-content, and highest upregulation was induced by an alginate with 19% single G residues. In the epidermis, CXCR7 expression was restricted to the basal layer. This study defines two biological effects of ultrapure alginates on KCs, both being dependent on the alginate structure, and being either dependent or independent of Ca.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, St. Olavs Hospital, N-7491 Trondheim, Norway. jorgen.stenvik@ntnu.no
authors.forename: Jørgen
authors.initials: J
authors.lastname: Stenvik
authors.forename: Håvard
authors.initials: H
authors.lastname: Sletta
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Grimstad
authors.forename: Brita
authors.initials: B
authors.lastname: Pukstad
authors.forename: Liv
authors.initials: L
authors.lastname: Ryan
authors.forename: Randi
authors.initials: R
authors.lastname: Aune
authors.forename: Wenche
authors.initials: W
authors.lastname: Strand
authors.forename: Anne
authors.initials: A
authors.lastname: Tøndervik
authors.forename: Sverre Helge
authors.initials: SH
authors.lastname: Torp
authors.forename: Gudmund
authors.initials: G
authors.lastname: Skjåk-Braek
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
mesh_terms: D000328:Adult; D000464:Alginates / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D048430:Cell Shape / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*
chemical_list: C501896:ACKR3 protein, human; D000464:Alginates; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D054387:Receptors, CXCR; D002118:Calcium