Abstract
Autophagy is a multistage catabolic process that mediates stress responses. However, the role of autophagy in epidermal proliferation, particularly under conditions when the epidermis becomes "activated" (hyperproliferative), remains unclear. We have shown that inhibition of Beclin 1, a key activator in the initiation phase of autophagy, attenuates imiquimod (IMQ)-induced epidermal hyperplasia in adult mice as well as naturally occurring hyperproliferation in neonatal mouse epidermis. Inhibition of Beclin 1 did not change the levels of several key inflammatory molecules or the numbers of immune cells in lesional skins. This indicates that autophagy does not affect inflammatory regulators in IMQ-treated mouse skin. Bioinformatic analysis combined with gene expression quantitative assays, revealed that a deficiency in autophagy decreases the expression of PDZ Binding Kinase (PBK), a regulator of the cell cycle, in mouse epidermis and human epidermal keratinocytes (HEKs). Interestingly, the decrease in PBK results in inhibition of proliferation in HEKs and such reduced proliferation can be rescued by activation of p38, the downstream signaling of PBK. Collectively, autophagy plays a positive role in epidermal proliferation, which is in part via regulating PBK expression.