1159 PCSK9 inhibition interrupts the cross talk between keratinocytes and macrophages and prevents UVB-induced skin damage

The study was aim to examine the role and mechanism of Proprotein convertase subtilisin/kexin type 9 (PCSK9) in ultraviolet B (UVB)-induced skin damage. PCSK9 is an enzyme that promotes degradation low-density lipoprotein receptors. It involved hyperlipidemia as well other diseases, such cancer inflammation. However, detail for on lesions not clear. Thus, we aimed possible action UVB-induced A small molecule inhibitor (SBC110736) against siRNA duplexes targeting mouse were designed applied. Their effects various UVB-activated proteins investigated. co-culture system using UVB-treated keratinocytes supernatant used stimulate macrophages observe its effect stimulator interferon genes (STING) pathway activation. Immunohistochemical staining revealed a significant increase expression after UVB exposure, indicating Skin damage, epidermal thickness, keratinocyte hyperproliferation significantly alleviated treatment with SBC110736 or duplexes, compared model group. Notably, exposure triggered DNA damage keratinocytes, whereas substantial regulatory factor 3 (IRF3) activation observed macrophages. In system, from induced IRF3 This inhibited by knockdown. Collectively, our findings reveal plays critical crosstalk between damaged STING interruption this inhibition may be potential therapeutic strategy