Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis
Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis
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角质形成细胞中半乳糖凝集素 3 的减少：潜在的诊断标志物和银屑病发病机制的关键因素
DOI：
10.1016/j.jaut.2017.11.002
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
王亮春
中科院分区：
文献类型：
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作者：
石臻睿;谭国珍;Cao cui xiang;韩艳芳;孟珍;Man Xiao yong;江泽鑫;张宇萍;Dang ning ning;Kai-Hua Wei;Ding-Fang Bu;Fu-Tong Liu;王亮春
银屑病特异性蛋白在角质形成细胞中的异常调节，并参与银屑病的病理生理过程仍然难以捉摸。我们在此报告了表皮Galectin-3在皮损皮肤中的表达显著下调，但在银屑病患者的非皮损皮肤中不表达，在临床和组织学上与银屑病相似的一组被称为银屑病样皮炎的疾病中也不表达。表皮Galectin-3的缺乏足以促进银屑病皮损的发展，证据是Galectin-3基因敲除(GAL3−/−)小鼠的皮肤炎症比野生型小鼠更严重，咪喹莫特治疗后，以及移植到野生型小鼠上的GAL3−/−小鼠的皮肤炎症更严重。银屑病样皮损的发生归因于：1)角质形成细胞中银屑病信号通过JNK途径自发增强；2)在Galectin-3表达受损的角质形成细胞中，由于S100A7-9和CXCL-1，8过表达而导致的中性粒细胞聚集。通过选择性CXCR2拮抗剂SB225002抑制中性粒细胞聚集和皮内注射重组Galectin-3，GAL-3−/−小鼠的牛皮癣样皮炎得到显著改善。总体而言，这些发现提供了与Galectin-3相关的牛皮癣诊断和治疗解决方案。
Psoriasis-specific proteins dysregulated in keratinocytes and involved in the pathophysiological process of psoriasis remains elusive. We report here that epidermal galectin-3 expression is significantly downregulated in lesional skin, but not in non-lesional skin in psoriasis patients, nor in a group of diseases known as psoriasiform dermatitis clinically and histologically similar to psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote development of psoriatic lesions, as evidenced by more severe skin inflammation in galectin-3 knockout (gal3−/−) mice, compared to wild-type mice, after imiquimod treatment, and in skin from gal3−/−mice grafted onto wildtype mice. The development of psoriatic-like lesions is attributable to 1) the spontaneously tuning up of psoriasis signatures in keratinocytes through JNK pathway; and 2) neutrophil accumulation caused by the enhanced leukocyte-recruiting capacity associated with overexpression of S100A7-9 and CXCL-1, 8 in keratinocytes with impaired galectin-3 expression. Psoriasis-like skin inflammation is significantly improved in gal-3−/−mice both by inhibition of neutrophils accumulation with a selective CXCR2 antagonist of SB225002, and by intracutaneous injection of recombinant galectin-3. Overall, these findings offer promising galectin-3-related diagnostic and therapeutic resolutions of psoriasis.