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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  ;  Jae Hee Cheon 
 Scientific Reports, Vol.9(1) : 11716, 2019 
Journal Title
 Scientific Reports 
Issue Date
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Park, Soo Jung(박수정)
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
Lee, Hyun Jung(이현정)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
Hwang, Inhwa(황인화) ORCID logo https://orcid.org/0000-0001-5235-3519
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