Academic Journal
The OSMR gene is involved in Hirschsprung associated enterocolitis susceptibility through an altered downstream signaling
| العنوان: | The OSMR gene is involved in Hirschsprung associated enterocolitis susceptibility through an altered downstream signaling |
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| المؤلفون: | Bachetti T., Rosamilia F., Bartolucci M., Santamaria G., Mosconi M., Sartori S., De Filippo M. R., Di Duca M., Obino V., Avanzini S., Mavilio D., Candiani S., Petretto A., Prato A. P., Ceccherini I., Lantieri F. |
| المساهمون: | T. Bachetti, F. Rosamilia, M. Bartolucci, G. Santamaria, M. Mosconi, S. Sartori, M.R. De Filippo, M. Di Duca, V. Obino, S. Avanzini, D. Mavilio, S. Candiani, A. Petretto, A.P. Prato, I. Ceccherini, F. Lantieri |
| بيانات النشر: | MDPI |
| سنة النشر: | 2021 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | gut inflammation, Hirschsprung Associated Enterocolitis (HAEC), mucosal immunity, Oncostatin-M receptor (OSMR), proteomic, Whole-Exome Sequencing (WES), allele, enterocoliti, gene expression, gene frequency, genetic variation, genotype, hirschsprung disease, human, models, molecular, oncostatin M receptor beta subunit, protein conformation, structure-activity relationship, whole exome sequencing, whole genome sequencing, disease susceptibility, signal transduction, Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio, Settore MED/04 - Patologia Generale, Settore MED/12 - Gastroenterologia, Settore MED/03 - Genetica Medica, Settore MED/38 - Pediatria Generale e Specialistica |
| الوصف: | Hirschsprung (HSCR) Associated Enterocolitis (HAEC) is a common life-threatening compli-cation in HSCR. HAEC is suggested to be due to a loss of gut homeostasis caused by impairment of immune system, barrier defense, and microbiome, likely related to genetic causes. No gene has been claimed to contribute to HAEC occurrence, yet. Genetic investigation of HAEC by Whole-Exome Sequencing (WES) on 24 HSCR patients affected (HAEC) or not affected (HSCR-only) by enterocolitis and replication of results on a larger panel of patients allowed the identification of the HAEC susceptibility variant p.H187Q in the Oncostatin-M receptor (OSMR) gene (14.6% in HAEC and 5.1% in HSCR-only, p = 0.0024). Proteomic analysis on the lymphoblastoid cell lines from one HAEC patient homozygote for this variant and one HAEC patient not carrying the variant revealed two well distinct clusters of proteins significantly up or downregulated upon OSM stimulation. A marked enrichment in immune response pathways (q < 0.0001) was shown in the HAEC H187 cell line, while proteins upregulated in the HAEC Q187 lymphoblasts sustained pathways likely involved in pathogen infection and inflammation. In conclusion, OSMR p.H187Q is an HAEC susceptibility variant and perturbates the downstream signaling cascade necessary for the gut immune response and homeostasis maintenance. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33917126; info:eu-repo/semantics/altIdentifier/wos/WOS:000644316800001; volume:22; issue:8; firstpage:1; lastpage:16; numberofpages:16; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/2434/860499; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85103641063 |
| DOI: | 10.3390/ijms22083831 |
| الاتاحة: | http://hdl.handle.net/2434/860499 https://doi.org/10.3390/ijms22083831 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D9B67980 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ijms22083831 |
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