PP2Acα regulates epidermal cell proliferation via the EGFR/AKT/mTOR pathway in psoriasis-like skin lesions caused by PPP2CA deficiency.

Abstract

Psoriasis, a common skin disease, endangers human physiological and mental health; however, its pathogenesis remains unclear. Keratinocyte proliferation is a typical pathological characteristic of psoriasis. Serine/threonine protein phosphatase 2A (PP2A) is one of the most important phosphatases for maintaining normal phosphorylation levels in humans. PP2Acα is the alpha subtype of the PP2A C subunit (encoded by PPP2CA), which maintains the catalytic functions of PP2A. Epidermal growth factor receptor (EGFR) is activated by phosphorylation (p-EGFR) to regulate the downstream signalling pathway to promote epidermal cell proliferation. Previous studies have found that PPP2CA induced epidermal hyperplasia, keratinization and other pathological phenomena similar to those in mouse models of psoriasis. The present study showed that PP2Acα negatively regulated EGFR phosphorylation and epidermal cell proliferation, and EGFR inhibitors could alleviate PP2Acα by inhibiting epidermal cell proliferation. This study further examined the effect of mechanisms on epidermal cell proliferation and the downstream signalling pathway of EGFR using molecular technological methods to explore new ideas for treating psoriasis.