Histatins, wound healing, and cell migration

Abstract

Wounds in the oral mucosa heal faster and more efficiently than those in the skin, although the mechanisms underlying these differences are not completely clear. In the last 10 years, a group of salivary peptides, the histatins, has gained attention on behalf of their ability to improve several phases of the wound-healing process. In addition to their roles as anti-microbial agents and in enamel maintenance, histatins elicit other biological effects, namely by promoting the migration of different cell types contained in the oral mucosa and in non-oral tissues. Histatins, and specifically histatin-1, promote cell adhesion and migration in oral keratinocytes, gingival and dermal fibroblasts, non-oral epithelial cells, and endothelial cells. This is particularly relevant, as histatin-1 promotes the re-epithelialization phase and the angiogenic responses by increasing epithelial and endothelial cell migration. Although the molecular mechanisms associated with histatin-dependent cell migration remain poorly understood, recent studies have pointed to the control of signaling endosomes and the balance of small GTPases. This review aimed to update the literature on the effects of histatins in cell migration, with a focus on wound healing. We will also discuss the consequences that this increasing field will have in disease and therapy design.

Histatin‐1 counteracts the cytotoxic and antimigratory effects of zoledronic acid in endothelial and osteoblast‐like cells

“…A through 2D). On the other hand, Histatin‐1 is known to promote cell migration in a wide variety of cell types (reviewed in ), thereby raising the possibility that it may also elicit its pro‐migratory effects in osteoblast‐like cells. As anticipated, Histatin‐1 promoted cell migration in both SAOS‐2 and MC3T3‐E1 cells (specifically a 1.3‐fold increase for SAOS‐2 and 1.4‐fold increase for MC3T3‐E1 cells, Fig.…”

“…Saliva is a source of multiple protective factors, among which Histatins have gained increasing attention, based on the simplicity of their structure, and the diversity of biologic effects that have been attributed to them (reviewed in ). Histatins are histidine‐rich peptides, commonly described as bactericidal and fungicidal .…”

Innate Inspiration: Antifungal Peptides and Other Immunotherapeutics From the Host Immune Response

“…Histatins comprise 12 structurally related members of which Hst-1 and Hst-3 are full-length proteins encoded by two genes, HTN1 (encoding Hst-1) and HTN3 (encoding Hst-3). The smaller proteins, Hst-2 (derived from Hst-1) and Hst-4 to−12 (derived from Hst-3), are generated by proteolytic cleavage of the parent Hst by salivary proteases during secretion (59,77,78). Histatins comprise 3 main HDP (Hst -1, -3 and -5), of which Hst-5 ( Figure 1A) has the most potent antifungal activity and can be found at concentrations of 15-30 µM in whole saliva (80).…”

“…Hst may also exert their antimicrobial activities by inhibiting host and microbial proteases and may attenuate tissue damage and microbial propagation during the onset of disease (63). Hst have other functions in the oral cavity, including acceleration of wound healing, tooth enamel mineral homeostasis and pellicle formation (78,98). Hst-1, -2 and -3, but not Hst-5, can promote re-epithelialization and angiogenesis during wound healing (78) and can prevent the translocation of bacteria across cell layers (99).…”

“…Whilst our understanding of the biology and function of AMP remains incomplete, especially how peptides behave in complex biological systems, we are gaining sufficient insight that researchers are increasingly making use of this biological knowledge and even computational approaches to design novel, synthetic AMP (278)(279)(280)(281)(282). Novel, informed drug-design approaches to identify AMP is aided by the vast sequence space available (78,283). Other approaches have taken known host defence peptides and attempted to optimise them using a variety of approaches (281,(284)(285)(286).…”