Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis

Zhen rui Shi, Guo zhen Tan, Cui xiang Cao, Yan fang Han, Zhen Meng, Xiao yong Man, Ze xin Jiang, Yu ping Zhang, Ning ning Dang, Kai hua Wei, Ding fang Bu, Fu-Tong Liu, Liangchun Wang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)30-40
Number of pages11
JournalJournal of Autoimmunity
Volume89
DOIs
StatePublished - May 1 2018
Externally publishedYes

Keywords

  • Galectin-3
  • Keratinocyte
  • Neutrophil
  • Pathogenesis
  • Psoriasis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Shi, Z. R., Tan, G. Z., Cao, C. X., Han, Y. F., Meng, Z., Man, X. Y., Jiang, Z. X., Zhang, Y. P., Dang, N. N., Wei, K. H., Bu, D. F., Liu, F-T., & Wang, L. (2018). Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis. Journal of Autoimmunity, 89, 30-40. https://doi.org/10.1016/j.jaut.2017.11.002