Ultraviolet B–Induced Skin Damage Is Mediated by Suppression of Protein Phosphatase 2B Activity

Calcineurin (Protein phosphatase 2B, PP2B) is a calcium-dependent serine/threonine phosphatase that regulates cellular survival and stress responses; however, its role in ultraviolet B (UVB)–induced skin damage remains incompletely understood. In the study, we investigated whether PP2B activity modulates UVB-induced apoptosis in skin. Normal epidermal keratinocytes (NHEKs) were exposed to UVB irradiation, followed by the assessment of intracellular Ca²⁺ levels, PP2B activity, and cell viability. At 8-12h post-irradiation, UVB significantly reduced intracellular Ca²⁺ concentration and PP2B activity in NHEKs, accompanied by a decrease in cell viability in NHEKs. Treatment with baicalein markedly attenuated UVB-induced apoptosis and restored PP2B activity. Notably, pharmacological inhibition of PP2B abrogated the cytoprotective effects of baicalein, as evidenced by reduced cell viability and increased caspase-3 activity. In an in vivo mouse model, baicalein administration significantly reduced epidermal thickness and the number of TUNEL-positive cells in UVB-irradiated dorsal skin. Consistently, caspase-3 expression was markedly decreased in baicalein-treated skin tissues following UVB exposure. Collectively, these findings demonstrate that UVB-induced keratinocyte apoptosis is associated with reduced PP2B activity, and that baicalein attenuates UVB-induced skin damage at least in part by preserving PP2B homeostasis. Our results identify PP2B as a critical regulator of UVB-induced skin injury, suggesting it as a potential therapeutic target for preventing photodamage.