Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis

作者：Madhusudan Grover, Simon J. Gibbons, Asha Nair, Cheryl E. Bernard, Adeel Zubair, Seth T. Eisenman, Laura 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 · 发表于：BMC Medical Genomics · 年份：2018 · DOI：10.1186/s12920-018-0379-1 · 被引用次数：54 · 研究领域：Gastrointestinal motility and disorders、Inflammatory Bowel Disease、Barrier Structure and Function Studies

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 log 2 fold 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 (log 2 fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonica...