Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis

doi:10.1172/JCI130740

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23344

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23344

Title:	Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis
Authors:	Chen, HL;Lo, CH;Huang, CC;Lu, MP;Hu, PY;Chen, CS;Chueh, DY;Chen, PL;Lin, TN;Lo, YH;Hsiao, YP;Hsu, DK;Liu, FT
Date:	2021
Issue Date:	2022-08-05T09:35:45Z (UTC)
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
ISSN:	0021-9738
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-alpha, 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.
URI:	http://dx.doi.org/10.1172/JCI130740 https://www.webofscience.com/wos/woscc/full-record/WOS:000607462600003 https://ir.csmu.edu.tw:8080/handle/310902500/23344
Relation:	JOURNAL OF CLINICAL INVESTIGATION ,2021,v131,issue 1
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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