P42 KLHDC7B participates in the mechanism of UVB treatment for psoriasis by regulating CHOP and the KEAP1/NRF2 pathway

Abstract Objective UVB phototherapy is an important method for the treatment of psoriasis, but the specific mechanism is unclear. KLHDC7B is a Kelch domain-containing protein that has been widely noted involving in multiple important cellular processes, but its expression and function in psoriasis remain to be further elucidated. The objective of this study was to explore the levels of KLHDC7B in psoriasis lesions and psoriasis keratinocytes with UVB irradiation. In addition, this study aimed to investigate whether KLHDC7B participates in the UVB treatment in patients with psoriasis. Methods We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting to determine the levels of KLHDC7B. QRT-PCR and ELISA were used to detect the secretion levels of IL-1β, CCL20 and CXCL10. Cell apoptosis was analysed by flow cytometric method. QRT-PCR and Western blotting were used to detect the expression of CHOP and KEAP1/NRF2 pathway. The results were statistically analysed by t-test. Results Our study showed a high expression of KLHDC7B in psoriasis lesions and keratinocytes stimulated with M5 for the psoriasis model. After UVB treatment, KLHDC7B was further increased. Knockdown of KLHDC7B reversed UVB-induced apoptosis and levels of IL-1β, CCL20 and CXCL10. Overexpression of KLHDC7B can improve the endoplasmic reticulum stress marker protein CHOP expression and NRF2 level. KLHDC7B could induce CHOP-mediated apoptosis and activate the KEAP1/NRF2 pathway to alleviate inflammation. In addition, we found that UVB promoted KLHDC7B expression through the nearby LncRNA called LncKLHDC7B-2. Conclusion KLHDC7B may act as a disease suppressor and play a key role in UVB treatment for psoriasis, which may provide a new target for treatment.