Cornulin Is Induced in Psoriasis Lesions and Promotes Keratinocyte Proliferation via Phosphoinositide 3-Kinase/Akt Pathways

The Journal of Investigative Dermatology
Changji LiYan Zheng

Abstract

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and infiltration of inflammatory cells. 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 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 five pro-inflammatory cytokines (i.e., IL-17A, 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 small interfering RNA suppressed G1/S transition and attenuated the M5-induced proliferation. In addition, CRNN overexpression increased the phosphorylation and activation of phosphoinositide 3-kinase and Akt. Inactivation of the phosphoinositide 3-kinase and Akt pathways using small interfering RNA 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 act...Continue Reading

Citations

Sep 6, 2020·The Journal of Investigative Dermatology·Musin KelelYungling L Lee
Jun 8, 2021·The Journal of Investigative Dermatology·Baochang LaiNanping Wang
Nov 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ivanka K KoychevaMilen I Georgiev
Dec 4, 2021·Journal of Cosmetic Dermatology·Wafaa Ahmed ShehataNanis S Holah
Jan 1, 2022·Journal of Clinical Pathology·Rajandeep KaurArnab Pal

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