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

  • J Autoimmun. 2018 May;89:30-40. doi: 10.1016/j.jaut.2017.11.002.
Zhen-Rui Shi  1 ,  Guo-Zhen Tan  1 ,  Cui-Xiang Cao  2 ,  Yan-Fang Han  1 ,  Zhen Meng  1 ,  Xiao-Yong Man  3 ,  Ze-Xin Jiang  1 ,  Yu-Ping Zhang  1 ,  Ning-Ning Dang  4 ,  Kai-Hua Wei  5 ,  Ding-Fang Bu  6 ,  Fu-Tong Liu  7 ,  Liangchun Wang  8
Affiliations
  • 1. Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • 2. Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Department of Dermatology, Guangzhou Red Cross Hospital, Guangzhou 510220, China.
  • 3. Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
  • 4. Department of Dermatology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, China.
  • 5. State Key Lab of Proteome, Beijing Proteome Research Center, Beijing 102206, China.
  • 6. Central Laboratory, Peking University First Hospital, Peking University, Beijing 100034, China.
  • 7. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • 8. Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: [email protected].
PMID: 29167025 DOI: 10.1016/j.jaut.2017.11.002
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.

Keywords
Galectin-3; Keratinocyte; Neutrophil; Pathogenesis; Psoriasis.
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