BIRC5 modulates keratinocyte proliferation and apoptosis via PI3K/AKT/mTOR-mediated autophagy

Psoriasis is characterized by abnormal keratinocyte proliferation and BIRC5, also known as survivin, plays a critical role in the pathogenesis of psoriasis. However, the regulatory role of BIRC5 in psoriasis progression remains unclear. To elucidate the mechanisms by which BIRC5 regulates psoriasis, we used a mouse model of imiquimod (IMQ)-induced psoriasis characterized by psoriasis area and severity index (PASI) scores and epidermal hyperplasia. Immunohistochemistry and western blotting were performed to assess cell proliferation, autophagy, and apoptosis in vivo. The M5 (Oncostatin-M, IL-22, TNF-α, IL-1α, and IL-17 A) was used to treat HaCaT cells for the psoriatic cell model. M5-triggered HaCaT cells were used to investigate the function of BIRC5 in cell proliferation, apoptosis, and autophagy in vitro. The deletion of BIRC5 alleviated IMQ-induced psoriasis-like skin lesions, reduced the PASI scores, and decreased epidermal thickness. Inhibition of BIRC5 suppressed proliferation, facilitated apoptosis, and activated autophagy in these IMQ-induced mice. Consistent with the animal experiment results, M5 accelerated the proliferation of HaCaT cells, whereas inhibited the apoptosis and autophagy of HaCaT cells; however, BIRC5 knockdown partially reversed these effects. Additionally, silencing BIRC5 inhibited the phosphorylation of PI3K, AKT, and mTOR. Furthermore, 3-MA or SC79 treatment negated the autophagy- and apoptosis-enhancing effect of BIRC5 inhibition, as well as the inhibitory effect on HaCaT cell proliferation. Collectively, BIRC5 may accelerate keratinocyte proliferation and inhibit keratinocyte apoptosis through PI3K/AKT/mTOR-mediated autophagy.