Proteomics-based functional studies reveal that galectin-3 plays a protective role in the pathogenesis of intestinal Behçet’s disease

Hyun Jung Lee, Jae Hyeon Kim, Sujeong Hong, Inhwa Hwang, Soo Jung Park, Tae Il Kim, Won Ho Kim, Je Wook Yu, Seung Won Kim, JaeHee Cheon

Research output: Contribution to journalArticle

Abstract

The pathogenesis of intestinal Behçet’s disease (BD) remains poorly understood. Therefore, we aimed to discover and validate biomarkers using proteomics analysis and subsequent functional studies. After two-dimensional electrophoresis, candidate proteins were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS). We validated these results by evaluating the protein levels and their functions in vitro using HT-29 colorectal cancer cells, colon tissues from patients and mice, and murine bone marrow derived macrophages (BMDMs). Of the 30 proteins differentially expressed in intestinal BD tissues, we identified seven using MALDI-TOF/TOF MS. Focusing on galectin-3, we found that TGF-B and IL-10 expression was significantly lower in shLGALS3-transfected cells. Expression of GRP78 and XBP1s and apoptosis rates were all higher in shLGALS3-transfected cells upon the induction of endoplasmic reticulum stress. In response to lipopolysaccharide stimulation, microtubule-associated protein 1 light chain 3B accumulated and lysosomes decreased in these cells. Finally, Salmonella typhimurium infection induced caspase-1 activation and increased IL-1β production, which facilitated activation of the NLRC4 inflammasome, in Lgals3−/− murine BMDMs compared to wild type BMDMs. Our data suggest that galectin-3 may play a protective role in the pathogenesis of intestinal BD via modulation of ER stress, autophagy, and inflammasome activation.

Original languageEnglish
Article number11716
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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Galectin 3
Intestinal Diseases
Proteomics
Inflammasomes
Macrophages
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Caspase 1
Proteins
Endoplasmic Reticulum Stress
Microtubule-Associated Proteins
Salmonella Infections
Autophagy
Salmonella typhimurium
Lysosomes
Interleukin-1
Interleukin-10
Colonic Neoplasms
Lipopolysaccharides
Electrophoresis
Colorectal Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lee, Hyun Jung ; Kim, Jae Hyeon ; Hong, Sujeong ; Hwang, Inhwa ; Park, Soo Jung ; Kim, Tae Il ; Kim, Won Ho ; Yu, Je Wook ; Kim, Seung Won ; Cheon, JaeHee. / Proteomics-based functional studies reveal that galectin-3 plays a protective role in the pathogenesis of intestinal Behçet’s disease. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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abstract = "The pathogenesis of intestinal Beh{\cc}et’s disease (BD) remains poorly understood. Therefore, we aimed to discover and validate biomarkers using proteomics analysis and subsequent functional studies. After two-dimensional electrophoresis, candidate proteins were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS). We validated these results by evaluating the protein levels and their functions in vitro using HT-29 colorectal cancer cells, colon tissues from patients and mice, and murine bone marrow derived macrophages (BMDMs). Of the 30 proteins differentially expressed in intestinal BD tissues, we identified seven using MALDI-TOF/TOF MS. Focusing on galectin-3, we found that TGF-B and IL-10 expression was significantly lower in shLGALS3-transfected cells. Expression of GRP78 and XBP1s and apoptosis rates were all higher in shLGALS3-transfected cells upon the induction of endoplasmic reticulum stress. In response to lipopolysaccharide stimulation, microtubule-associated protein 1 light chain 3B accumulated and lysosomes decreased in these cells. Finally, Salmonella typhimurium infection induced caspase-1 activation and increased IL-1β production, which facilitated activation of the NLRC4 inflammasome, in Lgals3−/− murine BMDMs compared to wild type BMDMs. Our data suggest that galectin-3 may play a protective role in the pathogenesis of intestinal BD via modulation of ER stress, autophagy, and inflammasome activation.",
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Proteomics-based functional studies reveal that galectin-3 plays a protective role in the pathogenesis of intestinal Behçet’s disease. / Lee, Hyun Jung; Kim, Jae Hyeon; Hong, Sujeong; Hwang, Inhwa; Park, Soo Jung; Kim, Tae Il; Kim, Won Ho; Yu, Je Wook; Kim, Seung Won; Cheon, JaeHee.

In: Scientific reports, Vol. 9, No. 1, 11716, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Lee, Hyun Jung

AU - Kim, Jae Hyeon

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AU - Hwang, Inhwa

AU - Park, Soo Jung

AU - Kim, Tae Il

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AU - Yu, Je Wook

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AU - Cheon, JaeHee

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