Title |
Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis
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Published in |
BMC Medical Genomics, August 2018
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DOI | 10.1186/s12920-018-0379-1 |
Pubmed ID | |
Authors |
Madhusudan Grover, Simon J. Gibbons, Asha A. Nair, Cheryl E. Bernard, Adeel S. Zubair, Seth T. Eisenman, Laura A. Wilson, Laura Miriel, Pankaj J. Pasricha, Henry P. Parkman, Irene Sarosiek, Richard W. McCallum, Kenneth L. Koch, Thomas L. Abell, William J. Snape, Braden Kuo, Robert J. Shulman, Travis J. McKenzie, Todd A. Kellogg, Michael L. Kendrick, James Tonascia, Frank A. Hamilton, Gianrico Farrugia, the NIDDK Gastroparesis Clinical Research Consortium (GpCRC) |
Abstract |
Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are still unclear. Diabetic gastroparetics, diabetic non-gastroparetic controls, idiopathic gastroparetics and non-diabetic non-gastroparetic controls underwent full-thickness gastric body biopsies. Deep RNA sequencing was performed and pathway analysis of differentially expressed transcripts was done using Ingenuity®. A subset of differentially expressed genes in diabetic gastroparesis was validated in a separate cohort using QT-PCR. 111 genes were differentially expressed in diabetic gastroparesis and 181 in idiopathic gastroparesis with a log2fold difference of | ≥ 2| and false detection rate (FDR) < 5%. Top canonical pathways in diabetic gastroparesis included genes involved with macrophages, fibroblasts and endothelial cells in rheumatoid arthritis, osteoarthritis pathway and differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F. Top canonical pathways in idiopathic gastroparesis included genes involved in granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Sixty-five differentially expressed genes (log2fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonical pathways associated with immune signaling. 4/5 highly differentially expressed genes (SGK1, APOLD1, CXCR4, CXCL2, and FOS) in diabetic gastroparesis were validated in a separate cohort of patients using RT-PCR. Immune profile analysis revealed that genes associated with M1 (pro inflammatory) macrophages were enriched in tissues from idiopathic gastroparesis tissues compared to controls (p < 0.05). Diabetic and idiopathic gastroparesis have both unique and overlapping transcriptomic signatures. Innate immune signaling likely plays a central role in pathogenesis of human gastroparesis. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 14 | 61% |
United Kingdom | 2 | 9% |
Unknown | 7 | 30% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 18 | 78% |
Scientists | 4 | 17% |
Practitioners (doctors, other healthcare professionals) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 6 | 16% |
Student > Bachelor | 4 | 11% |
Other | 3 | 8% |
Professor | 3 | 8% |
Student > Ph. D. Student | 3 | 8% |
Other | 6 | 16% |
Unknown | 13 | 34% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 10 | 26% |
Biochemistry, Genetics and Molecular Biology | 6 | 16% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 11% |
Nursing and Health Professions | 3 | 8% |
Neuroscience | 1 | 3% |
Other | 2 | 5% |
Unknown | 12 | 32% |