DDIT4 is an Innate Protector in Psoriatic Keratinocytes and 1,25(OH)2D3 Exerts Anti-Psoriasis Through Promoting DDIT4 Inducing Macro-Autophagy and Proliferation Inhibition

Abstract

Psoriasis vulgaris is a chronic inflammatory skin disorder. Its pathogenesis is now still unelucidated and the treatment is far from satisfied. DNA Damage-Inducible Transcript 4 (DDIT4) is a widely expressed protein in different tissue, which can activate cell macro-autophagy through mTORC1 passway. Vitamin D3 and analogues is a classic topical reagent for psoriasis vulgaris for more than 30 years, but its exact mechanism is not fully clear. In this study, we intend to verify whether vitamin D3 also exerts anti-psoriasis through promoting DDIT4 inducing macro-autophagy and proliferation inhibition in psoriasis vulgaris. Results showed DDIT4 was over-expressed in psoriatic tissue, and probably acted as an innate protector during psoriasis pathogenesis. 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) could promote DDIT4 expression in a rough linear correlation and subsequently activate macro-autophagy and inhabit cell proliferation, especially at the high concentration of 100nM. In terms of our understanding, this is the first time to reveal the interactions between 1,25(OH)2D3, DDIT4 and macro-autophagy in psoriasis vulgaris. DDIT4 is also probably a potential therapeutic target in future psoriatic treatments.