Academic Journal
HSPA6 is an ulcerative colitis susceptibility factor that is induced by cigarette smoke and protects intestinal epithelial cells by stabilizing anti-apoptotic Bcl-XL
| العنوان: | HSPA6 is an ulcerative colitis susceptibility factor that is induced by cigarette smoke and protects intestinal epithelial cells by stabilizing anti-apoptotic Bcl-XL |
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| المؤلفون: | Regeling, Anouk, Imhann, Floris, Volders, Haukeline H, Blokzijl, Tjasso, Bloks, Vincent W, Weersma, Rinse K, Dijkstra, Gerard, Faber, Klaas Nico |
| المصدر: | Regeling , A , Imhann , F , Volders , H H , Blokzijl , T , Bloks , V W , Weersma , R K , Dijkstra , G & Faber , K N 2016 , ' HSPA6 is an ulcerative colitis susceptibility factor that is induced by cigarette smoke and protects intestinal epithelial cells by stabilizing anti-apoptotic Bcl-XL ' , Biochimica et biophysica acta-Molecular basis of disease , vol. 1862 , no. 4 , pp. 788-796 . https://doi.org/10.1016/j.bbadis.2016.01.020 |
| سنة النشر: | 2016 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Ulcerative colitis, Cigarette smoke, Intestinal epithelium, Heat shock protein A6, Apoptosis, HEAT-SHOCK PROTEINS, INFLAMMATORY-BOWEL-DISEASE, ACID-INDUCED COLITIS, GASTROINTESTINAL-DISEASES, PHYSIOLOGICAL EXPRESSION, TRANSLATIONAL INHIBITION, COLON-CANCER, RISK LOCI, HEAT-SHOCK-PROTEIN-70, GERANYLGERANYLACETONE |
| الوصف: | BACKGROUND: Cigarette smoking ameliorates ulcerative colitis (UC) and aggravates Crohn's disease (CD). Cigarette smoke suppresses inflammation-induced apoptosis in intestinal epithelial cells (DLD-1), which may explain its protective effect in UC. Here, we performed transcriptome profiling of cigarette smoke extract (CSE)-exposed DLD-1 and Jurkat cells (T-lymphocytes) and related this to UC susceptibility genes with protective functions in the intestinal epithelium. METHODS: CSE-regulated genes in DLD-1 and Jurkat cells were identified by Illumina microarrays and compared to genes in UC susceptibility loci. Colon biopsies were analyzed by immunohistochemistry for cell-specific expression of HSPA6. CSE-induced gene expression was analyzed by Q-PCR, Western blotting and immunofluorescence microscopy. Protein (HSPA6/Bcl-XL) interactions were analyzed by immunoprecipitation. RESULTS: CSE changed the expression of 536 and 2560 genes in DLD-1 and Jurkat cells, respectively. The "response to unfolded protein" was one of the most significantly affected gene sets with prominent induction (20.3-fold) of heat shock protein A6 (HSPA6). Six CSE-induced genes in DLD-1 cells were located in UC-susceptibility loci, including HSPA6 (rs1801274). HSPA6 is highly expressed in the human colonic epithelium. CSE caused a dose-dependent strong (>100-fold at 30% CSE for 6h), but transient induction of HSPA6 mRNA and protein in DLD-1 cells. HSPA6 co-immune precipitated with anti-apoptotic Bcl-XL, protein levels of which were increased while mRNA levels were unchanged. CONCLUSIONS: HSPA6 is a cigarette smoke-induced UC-susceptibility gene. The HSPA6 risk locus is associated with decreased HSPA6 expression. HSPA6 provides epithelial protection by stabilizing anti-apoptotic Bcl-XL, thereby contributing to the beneficial effect of cigarette smoking in UC. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1016/j.bbadis.2016.01.020 |
| الاتاحة: | https://hdl.handle.net/11370/1af4176f-739d-4595-9dec-5666a83fdd06 https://research.rug.nl/en/publications/1af4176f-739d-4595-9dec-5666a83fdd06 https://doi.org/10.1016/j.bbadis.2016.01.020 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1338B4A1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.bbadis.2016.01.020 |
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