Histatin-1, a histidine-rich peptide in human saliva, promotes cell-substrate and cell-cell adhesion

Abstract

Histatins (Hsts) are histidine-rich peptides exclusively present in the saliva of higher primates. In this study, we explored the effects of Hsts on cell-substrate and cell-cell adhesion. Histatin (Hst)-1 caused a significant (>2-fold) increase (EC 50 = 1 mM) in the ability of human adherent cells to attach and spread, even in conditions that impaired cell spreading. Other tested Hsts did not stimulate cell spreading, indicating a specific effect of Hst1. The effect of Hst1 on cell-cell adhesion was investigated by using transepithelial resistance (TER) measurements in the human cell line Caco-2, a widely used model for the epithelial layer. We found that 10 mM Hst1 caused a 20% increase in TER compared to the negative control, indicating a function for Hst1 in intercellular cell adhesion and epithelial integrity. A role for Hst1 in both cellsubstrate and cell-cell adhesion is highly conceivable, because these 2 modes of adhesion are closely related via shared components and connected signaling pathways.-Van Dijk, I. A., Nazmi, K., Bolscher, J. G. M., Veerman, E. C. I., Stap, J. Histatin-1, a histidine-rich peptide in human saliva, promotes cell-substrate and cell-cell adhesion. FASEB J. 29, 3124-3132 (2015). www.fasebj.org

All‐trans retinoic acid and human salivary histatin‐1 promote the spreading and osteogenic activities of pre‐osteoblasts in vitro

“…However, due to the large variety of biomaterials, there is still an apparent great need for broadly applicable approaches to promote cell spreading on biomaterials. Previously, we and others showed that Hst1 promoted adhesion, spreading, and migration of various epithelial cells from different origins, such as mucosa , gingiva , cornea , and skin , endothelial cells , and osteogenic cells . All together, these findings underline a non‐cell type‐specific character of Hst1 rendering a promising application potential for tissue engineering purposes.…”

“…A promising candidate cell‐targeting agent to promote cell–substrate interactions is histatin‐1 (Hst1), a member of a large histidine‐rich salivary peptide family. Our previous findings show that Hst1 can significantly promote the attachment, spreading, and migration of various cell types including epithelial, endothelial, and osteogenic cells . Our recent data confirm that Hst1 can promote the spreading of osteogenic cells on both bio‐inert glass and titanium surface , which suggests a promising application potential of Hst1 in the cell‐based bone tissue engineering.…”

Effects of histatin-1 peptide on human corneal epithelial cells

“…Moreover, it has been reported that an unidentified GPCR pathway (Galpha-i linked) is critical for histatin peptide effects on cell migration [20]. Studies in other tissues on MAPK pathways have demonstrated an increase in cell-substrate and cell-cell adhesion with increased trans-epithelial resistance [21] and independence from p38 MAPK (proliferative) pathway inhibitors [7]. …”

Saliva-Derived Host Defense Peptides Histatin1 and LL-37 Increase Secretion of Antimicrobial Skin and Oral Mucosa Chemokine CCL20 in an IL-1α-Independent Manner

“…We have previously shown that histatins (Hst1 and Hst2) are the main factors in human saliva responsible for skin and oral keratinocyte and fibroblast migration, suggesting a role in wound closure [14–16]. Hst1 is also able to enhance cell-substrate adhesion and cell-cell interaction [17, 18]. …”