Anoctamin1 Induces Hyperproliferation of HaCaT Keratinocytes and Triggers Imiquimod-Induced Psoriasis-Like Skin Injury in Mice

• Published in: International journal of molecular sciences 2021-07, Vol.22 (13), p.7145
• Main Authors: Choi, Mi Ran, Kim, Hae Dong, Cho, Sinyoung, Jeon, Seong Ho, Kim, Dong Hyun, Wee, Jungwon, Yang, Young Duk
• Format: Article
• Language: English
• Subjects: Acids; AKT protein; Antiviral drugs; Arthritis; Breast cancer; Cell growth; Cell proliferation; Colorectal cancer; Cytokines; Disease; Ear; Erythema; Hyperplasia; IL-1β; Imiquimod; Immune system; Inflammation; Interleukin 22; Interleukin 23; Interleukin 6; Keratinocytes; Metabolic disorders; Pathophysiology; Phosphorylation; Prostate; Proteins; Psoriasis; Psoriatic arthritis; Signs and symptoms; Skin diseases; Skin injuries; Smooth muscle; Thickening; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22137145

Psoriasis, a long-lasting and multifactorial skin disease, is related to comorbidities such as metabolic disease, depression, and psoriatic arthritis. Psoriasis occurs due to a variety of factors including keratinocyte hyperproliferation, inflammation, and abnormal differentiation. Proinflammatory cytokines upregulated by increased activation of keratinocytes and immune cells in the skin trigger progression of psoriasis. This study aimed to investigate the effects of anoctamin1 (ANO1) on psoriasis development in vitro and in vivo. We analyzed the proliferation of HaCaT keratinocytes and ANO1-related ERK and AKT signaling pathways after ANO1 inhibitor (T16Ainh-A01 and Ani9) treatment and knock-down of ANO1. Furthermore, after applying imiquimod (IMQ) cream or coapplying IMQ cream and T16Ainh-A01 on mouse ears, we not only observed psoriatic symptoms, including ear thickening, but also quantified the effects of treatment on ERK and AKT signaling-involved proteins and proinflammatory cytokines. Inhibition of ANO1 attenuated the proliferation of HaCaT cells and induced reduction of pERK1/2. Coapplication of IMQ and T16Ainh-A01 on ears of mice reduced not only symptoms of IMQ-induced psoriasis such as thickening and erythema, but also expression of ANO1 and pERK1/2 compared to that of application of IMQ alone. In addition, the expression levels of IL-17A, IL-17F, IL-22, IL-23, IL-6, IL-1β, and TNF-α increased after applying IMQ and were significantly reduced by coapplying IMQ and T16Ainh-A01. These results aid in understanding the underlying mechanisms of ANO1 in epidermal layer keratinocyte hyperproliferation and suggest the potential of ANO1 as a target to treat psoriasis.