Proteomics in gastroparesis: unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

作者：Madhusudan Grover, Surendra Dasari, Cheryl E. Bernard, Lakshmikanth L. Chikkamenahalli, Katherine P. Yates, Pankaj J. Pasricha, Irene Sarosiek, Richard W. McCallum, Kenneth L. Koch, Thomas L. Abell, Braden Kuo, Robert J. Shulman, Simon J. Gibbons, Travis J. McKenzie, Todd A. Kellogg, Michael L. Kendrick, James Tonascia, Frank A. Hamilton, Henry P. Parkman, Gianrico Farrugia · 发表于：American Journal of Physiology-Gastrointestinal and Liver Physiology · 年份：2019 · DOI：10.1152/ajpgi.00115.2019 · 被引用次数：41 · 研究领域：Polysaccharides and Plant Cell Walls、Gastrointestinal motility and disorders、Endoplasmic Reticulum Stress and Disease

Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected P < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 × 10 −9 ; IG FDR = 6.3 × 10 −12 ]. In DG, properdin expression correlated with GCSI bloating ( r = −0.99, FDR = 0.02)...