title: In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37.
abstract: The human antimicrobial peptide LL-37 plays an important role in host defense against infection. In addition to its antimicrobial action, other activities have been described in eukaryotic cells that may contribute to the healing response. In this study, we demonstrated that in vitro human cathelicidin activates migration of the human keratinocyte cell line HaCaT, involving phenotypic changes related to actin dynamics and associated to augmented tyrosine phosphorylation of proteins involved in focal adhesion complexes, such as focal adhesion kinase and paxillin. Other events involved in the LL-37 response were the induction of the Snail and Slug transcription factors, activation of matrix metalloproteinases and activation of the mitogen-activated protein kinase , and phosphoinositide 3-kinase/Akt signaling pathways. These signaling events could be mediated not only through the transactivation of EGFR but also through the induction of G-protein-coupled receptor FPRL-1 expression in these cells. Finally, by in vivo adenoviral transfer of the antimicrobial peptide to excisional wounds in ob/ob mice, we demonstrated that LL-37 significantly improved re-epithelialization and granulation tissue formation. The protective and regenerative activities of LL-37 support its therapeutic potential to promote wound healing.
authors.affiliation: Regenerative Medicine Unit, Epithelial Biomedicine Division, Basic Research Department, CIEMAT-CIBERER, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Carretero
authors.forename: María J
authors.initials: MJ
authors.lastname: Escámez
authors.forename: Marta
authors.initials: M
authors.lastname: García
authors.forename: Blanca
authors.initials: B
authors.lastname: Duarte
authors.forename: Almudena
authors.initials: A
authors.lastname: Holguín
authors.forename: Luisa
authors.initials: L
authors.lastname: Retamosa
authors.forename: Jose L
authors.initials: JL
authors.lastname: Jorcano
authors.forename: Marcela Del
authors.initials: MD
authors.lastname: Río
authors.forename: Fernando
authors.initials: F
authors.lastname: Larcher
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000502:physiology*; D054804:Cathelicidins; D002460:Cell Line; D002465:Cell Movement; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004848:Epithelium / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D005260:Female; D022001:Focal Adhesions; D006097:Granulation Tissue / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000502:physiology; D044067:Receptors, Lipoxin / Q000235:genetics / Q000502:physiology; D012038:Regeneration; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology; D014945:Wound Healing