Cornulin Is Induced in Psoriasis Lesions and Promotes Keratinocyte Proliferation via PI3K-Akt Pathways.

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and infiltration of inflammatory cells. Cornulin (CRNN) is a major component of the cornified cell envelope and implicated in several epithelial malignancies. Here, we show that CRNN expression was increased in the lesioned epidermis from the patients with psoriasis vulgaris and the skin lesions from the imiquimod (IMQ)-treated mice. Expression of CRNN in cultured keratinocytes (HEKa and HaCaT) was also induced by M5, a mixture of 5 pro-inflammatory cytokines including IL-17Α, IL-22, IL-1α, Oncostatin M and TNF-α. Lentiviral expression of CRNN increased cell proliferation by inducing Cyclin D1. Conversely, Knockdown of CRNN by siRNA suppressed G1/S transition and attenuated the M5-induced proliferation. In addition, CRNN overexpression increased the phosphorylation and activation of phosphoinositide 3-kinase (PI3K) and Akt. Inactivation of the PI3K and Akt pathways using siRNA or selective inhibitors (LY294002 and MK2206) reduced the proliferative effects of CRNN. Furthermore, topical use of anti-psoriatic calcipotriol effectively decreased expression of CRNN, inhibited the Akt activation and improved the IMQ-stimulated psoriasis-like pathologies. Taken together, these results suggest that induced expression of CRNN may contribute to the pathogenesis of psoriasis.