Phloridzin isolated from Acanthopanax senticosus promotes proliferation of α6 integrin (CD 49f) and β1 integrin (CD29) enriched for a primary keratinocyte population through the ERK-mediated mTOR pathway

We investigated the proliferative effect of a Acanthopanax senticosus extract (ASE) on human CD49f⁺/CD29⁺ keratinocytes and isolated phloridzin from A. senticosus as an active compound. In addition, the possible mechanisms of action were examined. We found that the ASE and phloridzin-promoted proliferation of CD49f⁺/CD29⁺ cells using MTT and Click-iT™ EdU flow cytometry assays. In addition, phosphorylation of the p44/42 MAPK (ERK), mTOR, p70 S6 kinase (p70S6K), S6 ribosomal protein (S6RP), eukaryotic initiation factor 4B (eIF4B), and eIF4E was stepwise induced in CD49f⁺/CD29⁺ cells. Furthermore, the ASE and phloridzin significantly induced the production of vascular endothelial growth factor and interleukin-6 in CD49f⁺/CD29⁺ cells. Similarly, ASE and phloridzin-induced phosphorylation of the mTOR/p70S6K/S6RP/eIF4B/eIF4E pathway was blocked in response to pretreatment with PD98059, a specific ERK inhibitor. Taken together, these results indicate that ASE and phloridzin-induced proliferation of CD49f⁺/CD29 ⁺ cells under serum-free conditions was mediated by the ERK-dependent mTOR pathway.