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

5 Citations (Scopus)

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

Fingerprint

Galectin 3
Keratinocytes
Psoriasis
Skin
Knockout Mice
imiquimod
Neutrophils
Inflammation
MAP Kinase Signaling System
Dermatitis
Leukocytes
Down-Regulation
Injections
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Decrease of galectin-3 in keratinocytes : A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis. / Shi, Zhen rui; Tan, Guo zhen; Cao, Cui xiang; Han, Yan fang; Meng, Zhen; Man, Xiao yong; Jiang, Ze xin; Zhang, Yu ping; Dang, Ning ning; Wei, Kai hua; Bu, Ding fang; Liu, Fu-Tong; Wang, Liangchun.

In: Journal of Autoimmunity, Vol. 89, 01.05.2018, p. 30-40.

Research output: Contribution to journalArticle

Shi, ZR, Tan, GZ, Cao, CX, Han, YF, Meng, Z, Man, XY, Jiang, ZX, Zhang, YP, Dang, NN, Wei, KH, Bu, DF, 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, vol. 89, pp. 30-40. https://doi.org/10.1016/j.jaut.2017.11.002
Shi, Zhen rui ; Tan, Guo zhen ; Cao, Cui xiang ; Han, Yan fang ; Meng, Zhen ; Man, Xiao yong ; Jiang, Ze xin ; Zhang, Yu ping ; Dang, Ning ning ; Wei, Kai hua ; Bu, Ding fang ; Liu, Fu-Tong ; Wang, Liangchun. / Decrease of galectin-3 in keratinocytes : A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis. In: Journal of Autoimmunity. 2018 ; Vol. 89. pp. 30-40.
@article{b4485a7dab384f02967387a617494d8a,
title = "Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis",
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",
author = "Shi, {Zhen rui} and Tan, {Guo zhen} and Cao, {Cui xiang} and Han, {Yan fang} and Zhen Meng and Man, {Xiao yong} and Jiang, {Ze xin} and Zhang, {Yu ping} and Dang, {Ning ning} and Wei, {Kai hua} and Bu, {Ding fang} and Fu-Tong Liu and Liangchun Wang",
year = "2018",
month = "5",
day = "1",
doi = "10.1016/j.jaut.2017.11.002",
language = "English (US)",
volume = "89",
pages = "30--40",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Decrease of galectin-3 in keratinocytes

T2 - A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis

AU - Shi, Zhen rui

AU - Tan, Guo zhen

AU - Cao, Cui xiang

AU - Han, Yan fang

AU - Meng, Zhen

AU - Man, Xiao yong

AU - Jiang, Ze xin

AU - Zhang, Yu ping

AU - Dang, Ning ning

AU - Wei, Kai hua

AU - Bu, Ding fang

AU - Liu, Fu-Tong

AU - Wang, Liangchun

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

KW - Galectin-3

KW - Keratinocyte

KW - Neutrophil

KW - Pathogenesis

KW - Psoriasis

UR - http://www.scopus.com/inward/record.url?scp=85034587798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034587798&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2017.11.002

DO - 10.1016/j.jaut.2017.11.002

M3 - Article

C2 - 29167025

AN - SCOPUS:85034587798

VL - 89

SP - 30

EP - 40

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

ER -