Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China; Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China; Department of Dermatology, Jiuquan City People's Hospital, Jiuquan, China.
Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.
J Invest Dermatol. 2019 Jan;139(1):71-80. doi: 10.1016/j.jid.2018.06.184. Epub 2018 Sep 25.
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 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.
银屑病是一种慢性炎症性皮肤病，其特征为表皮角质形成细胞的异常增殖和炎症细胞的浸润。CRNN 是角化细胞包膜的主要成分，与几种上皮恶性肿瘤有关。在这里，我们显示寻常型银屑病患者皮损和咪喹莫特（IMQ）处理的小鼠皮肤病变中 CRNN 的表达增加。五种促炎细胞因子（即 IL-17A、IL-22、IL-1α、oncostatin M 和 TNF-α）混合物 M5 也诱导培养角质形成细胞（HEKa 和 HaCaT）中 CRNN 的表达。CRNN 的慢病毒表达通过诱导细胞周期蛋白 D1 增加细胞增殖。相反，通过小干扰 RNA 敲低 CRNN 抑制 G1/S 转换并减弱 M5 诱导的增殖。此外，CRNN 过表达增加了磷酸肌醇 3-激酶和 Akt 的磷酸化和激活。使用小干扰 RNA 或选择性抑制剂（LY294002 和 MK2206）抑制磷酸肌醇 3-激酶和 Akt 途径的失活降低了 CRNN 的增殖作用。此外，局部使用抗银屑病的钙泊三醇可有效降低 CRNN 的表达，抑制 Akt 激活并改善 IMQ 刺激的银屑病样病理。总之，这些结果表明诱导的 CRNN 表达可能有助于银屑病的发病机制。
