SLC35E1 promotes keratinocyte proliferation in psoriasis by regulating zinc homeostasis

作者：Tao Huang, Shijun Chen, Ke Ding, Baoqing Zheng, Weiqi Lv, Xiaobo Wang, Xiaobo Wang, Yadan Zhong, Hongxin Huang, Xin Zhang, Shufeng Ma, Xiaohua Wang, Xiaohua Wang, Xiaohua Wang, Zhili Rong · 发表于：Cell Death and Disease · 年份：2023 · DOI：10.1038/s41419-023-05874-1 · 被引用次数：13 · 研究领域：Psoriasis: Treatment and Pathogenesis、Immunodeficiency and Autoimmune Disorders、Retinoids in leukemia and cellular processes

Abstract Keratinocyte hyperproliferation is a key pathogenic factor in psoriasis. However, the mechanisms that regulate keratinocyte hyperproliferation in this condition remain unclear. Here, we found that SLC35E1 was highly expressed in keratinocytes of patients with psoriasis and that Slc35e1 − / − mice displayed a less severe imiquimod (IMQ)-induced psoriasis-like phenotype than their wild-type siblings. In addition, SLC35E1 deficiency inhibited keratinocyte proliferation in both mice and cultured cells. On a molecular level, SLC35E1 was found to regulate zinc ion concentrations and subcellular localization, while zinc ion chelation reversed the IMQ-induced psoriatic phenotype in Slc35e1 − / − mice. Meanwhile, epidermal zinc ion levels were decreased in patients with psoriasis and zinc ion supplementation alleviated the psoriatic phenotype in an IMQ-induced mouse model of psoriasis. Our results indicated that SLC35E1 can promote keratinocyte proliferation by regulating zinc ion homeostasis and zinc ion supplementation has potential as a therapy for psoriasis.