PMID- 31406212 OWN - NLM STAT- MEDLINE DCOM- 20201026 LR - 20211204 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 9 IP - 1 DP - 2019 Aug 12 TI - Proteomics-based functional studies reveal that galectin-3 plays a protective role in the pathogenesis of intestinal Behcet's disease. PG - 11716 LID - 10.1038/s41598-019-48291-1 [doi] LID - 11716 AB - The pathogenesis of intestinal Behcet'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-1beta 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. FAU - Lee, Hyun Jung AU - Lee HJ AD - Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. AD - Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. FAU - Kim, Jae Hyeon AU - Kim JH AUID- ORCID: 0000-0003-0064-6656 AD - Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. AD - Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. FAU - Hong, Sujeong AU - Hong S AD - Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. FAU - Hwang, Inhwa AU - Hwang I AD - Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. FAU - Park, Soo Jung AU - Park SJ AUID- ORCID: 0000-0003-0699-6809 AD - Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Tae Il AU - Kim TI AUID- ORCID: 0000-0003-4807-890X AD - Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Won Ho AU - Kim WH AD - Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. FAU - Yu, Je-Wook AU - Yu JW AD - Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Seung Won AU - Kim SW AD - Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. swk21c@hanmail.net. AD - Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. swk21c@hanmail.net. AD - Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. swk21c@hanmail.net. FAU - Cheon, Jae Hee AU - Cheon JH AD - Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. GENIUSHEE@yuhs.ac. AD - Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. GENIUSHEE@yuhs.ac. AD - Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. GENIUSHEE@yuhs.ac. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190812 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Blood Proteins) RN - 0 (Calcium-Binding Proteins) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (Galectin 3) RN - 0 (Galectins) RN - 0 (HSPA5 protein, human) RN - 0 (Heat-Shock Proteins) RN - 0 (Hspa5 protein, mouse) RN - 0 (IL1B protein, mouse) RN - 0 (Interleukin-1beta) RN - 0 (Ipaf protein, mouse) RN - 0 (LGALS3 protein, human) RN - 0 (Lipopolysaccharides) RN - 0 (Proteome) RN - 0 (RNA, Small Interfering) RN - 0 (Transforming Growth Factor beta) RN - 0 (X-Box Binding Protein 1) RN - 0 (Xbp1 protein, mouse) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Apoptosis Regulatory Proteins/genetics/immunology MH - Behcet Syndrome/genetics/*immunology/pathology MH - Blood Proteins MH - Calcium-Binding Proteins/genetics/immunology MH - Endoplasmic Reticulum Chaperone BiP MH - Epithelial Cells/drug effects/*immunology/pathology MH - Female MH - Galectin 3/antagonists & inhibitors/genetics/*immunology MH - Galectins MH - Gene Expression Regulation MH - HT29 Cells MH - Heat-Shock Proteins/genetics/immunology MH - Humans MH - Interleukin-10/genetics/immunology MH - Interleukin-1beta/genetics/immunology MH - Intestines/drug effects/*immunology/pathology MH - Lipopolysaccharides/pharmacology MH - Lysosomes/drug effects/metabolism MH - Macrophages/drug effects/immunology MH - Mice MH - Mice, Inbred C57BL MH - Primary Cell Culture MH - Proteome/genetics/*immunology MH - RNA, Small Interfering/genetics/metabolism MH - Transforming Growth Factor beta/genetics/immunology MH - X-Box Binding Protein 1/genetics/immunology PMC - PMC6691011 COIS- The authors declare no competing interests. EDAT- 2019/08/14 06:00 MHDA- 2020/10/27 06:00 PMCR- 2019/08/12 CRDT- 2019/08/14 06:00 PHST- 2019/01/29 00:00 [received] PHST- 2019/06/17 00:00 [accepted] PHST- 2019/08/14 06:00 [entrez] PHST- 2019/08/14 06:00 [pubmed] PHST- 2020/10/27 06:00 [medline] PHST- 2019/08/12 00:00 [pmc-release] AID - 10.1038/s41598-019-48291-1 [pii] AID - 48291 [pii] AID - 10.1038/s41598-019-48291-1 [doi] PST - epublish SO - Sci Rep. 2019 Aug 12;9(1):11716. doi: 10.1038/s41598-019-48291-1.