摘要BACKGROUNDThe histatin (Hst) peptide family, which comprises at least 12 small, cationic and histidine-rich peptides, is mainly found in the saliva of higher primates.1 According to their functional characteristics, the Hst family is divided into two major groups:(1) antimicrobial Hsts (e.g., Hst5)2–5 and (2) cell-activating Hsts (e.g., Hst1 and Hst2).6–9 Hst1 and Hst2 can promote a large number of cell activities, such as adhesion, migration, cell-cell adhesion, differentiation and angiogenesis.6–12 With these functions, Hsts play important roles in protecting oral mucosa and maintaining its homeostasis.8,11,13 Previous findings indicate that the cell-activating effects of Hst1 and Hst2 can be abolished by both the specific inhibitors of G protein-coupled receptors (GPCR) and extracellular signal-regulated kinases 1/2 (ERK1/2) pathway.7,14 Moreover, our recent study has shown that within 5 min after administration to cells, both Hst1 and Hst2 are quickly taken up and targeted to mitochondria and endoplasmic reticulum (ER) in vitro.