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- Title
Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis.
- Authors
Hung-Lin Chen; Chia-Hui Lo; Chi-Chun Huang; Meng-Ping Lu; Po-Yuan Hu; Chang-Shan Chen; Di-Yen Chueh; Peilin Chen; Teng-Nan Lin; Yuan-Hsin Lo; Yu-Ping Hsiao; Hsu, Daniel K.; Fu-Tong Liu; Chen, Hung-Lin; Lo, Chia-Hui; Huang, Chi-Chun; Lu, Meng-Ping; Hu, Po-Yuan; Chen, Chang-Shan; Chueh, Di-Yen
- Abstract
Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis.
- Subjects
KERATINOCYTES; PSORIASIS; SKIN inflammation; PATHOLOGY; INTRADERMAL injections
- Publication
Journal of Clinical Investigation, 2021, Vol 131, Issue 1, p1
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI130740