The salivary peptide histatin‐1 promotes endothelial cell adhesion, migration, and angiogenesis

The FASEB JournalVolume 31, Issue 11 p. 4946-4958 ResearchFree to Read The salivary peptide histatin-1 promotes endothelial cell adhesion, migration, and angiogenesis Pedro Torres, Pedro Torres Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, ChileSearch for more papers by this authorJorge Díaz, Jorge Díaz Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, ChileSearch for more papers by this authorMaximiliano Arce, Maximiliano Arce Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, Chile Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, ChileSearch for more papers by this authorPatricio Silva, Patricio Silva Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, Chile Faculty of Health Sciences, Universidad Central de Chile, Santiago, ChileSearch for more papers by this authorPablo Mendoza, Pablo Mendoza Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, ChileSearch for more papers by this authorPablo Lois, Pablo Lois Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileSearch for more papers by this authorAlfredo Molina-Berríos, Alfredo Molina-Berríos Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, ChileSearch for more papers by this authorGareth I. Owen, Gareth I. Owen Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, Chile Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, ChileSearch for more papers by this authorVerónica Palma, Verónica Palma Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileSearch for more papers by this authorVicente A. Torres, Corresponding Author Vicente A. Torres [email protected] Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, Chile Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, Chile Correspondence: Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Calle Sergio Livingstone 943, Independencia, Santiago 8380-492, Chile. E-mail: [email protected]Search for more papers by this author Pedro Torres, Pedro Torres Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, ChileSearch for more papers by this authorJorge Díaz, Jorge Díaz Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, ChileSearch for more papers by this authorMaximiliano Arce, Maximiliano Arce Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, Chile Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, ChileSearch for more papers by this authorPatricio Silva, Patricio Silva Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, Chile Faculty of Health Sciences, Universidad Central de Chile, Santiago, ChileSearch for more papers by this authorPablo Mendoza, Pablo Mendoza Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, ChileSearch for more papers by this authorPablo Lois, Pablo Lois Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileSearch for more papers by this authorAlfredo Molina-Berríos, Alfredo Molina-Berríos Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, ChileSearch for more papers by this authorGareth I. Owen, Gareth I. Owen Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, Chile Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, ChileSearch for more papers by this authorVerónica Palma, Verónica Palma Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileSearch for more papers by this authorVicente A. Torres, Corresponding Author Vicente A. Torres [email protected] Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, Chile Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, Chile Correspondence: Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Calle Sergio Livingstone 943, Independencia, Santiago 8380-492, Chile. E-mail: [email protected]Search for more papers by this author First published: 27 July 2017 https://doi.org/10.1096/fj.201700085RCitations: 10Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Saliva is a key factor that contributes to the high efficiency of wound healing in the oral mucosa. This is not only attributed to physical cues but also to the presence of specific peptides in the saliva, such as histatins. Histatin-1 is a 38 aa antimicrobial peptide, highly enriched in human saliva, which has been previously reported to promote the migration of oral keratinocytes and fibroblasts in vitro. However, the participation of histatin-1 in other crucial events required for wound healing, such as angiogenesis, is unknown. Here we demonstrate that histatin-1 promotes angiogenesis, as shown in vivo, using the chick chorioallantoic membrane model, and by an in vitro tube formation assay, using both human primary cultured endothelial cells (HUVECs) and the EA.hy926 cell line. Specifically, histatin-1 promoted endothelial cell adhesion and spreading onto fibronectin, as well as endothelial cell migration in the wound closure and Boyden chamber assays. These actions required the activation of the Ras and Rab interactor 2 (RIN2)/Rab5/Rac1 signaling axis, as histatin-1 increased the recruitment of RIN2, a Rab5–guanine nucleotide exchange factor (GEF) to early endosomes, leading to sequential Rab5/Rac1 activation. Accordingly, interfering with either Rab5 or Rac1 activities prevented histatin-1-dependent endothelial cell migration. Finally, by immunodepletion assays, we showed that salivary histatin-1 is required for the promigratory effects of saliva on endothelial cells. In conclusion, we report that salivary histatin-1 is a novel proangiogenic factor that may contribute to oral wound healing.—Torres, P., Díaz, J., Arce, M., Silva, P., Mendoza, P., Lois, P., Molina-Berrios, A., Owen, G. I., Palma, V., Torres, V. A. The salivary peptide histatin-1 promotes endothelial cell adhesion, migration, and angiogenesis. FASEB J. 31, 4946–4958 (2017). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2fj201700085r-sup-0001.pdfPDF document, 244.9 KB Supplementary Material fsb2fj201700085r-sup-0002.aviapplication/avi, 3.2 MB Supplementary Material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume31, Issue11November 2017Pages 4946-4958 RelatedInformation