Proteomic analysis of the intestine reveals SNARE-mediated immunoregulatory and amino acid absorption perturbations in a rat model of depression
LIFE SCIENCES
Authors: Gong, Xue; Huang, Cheng; Yang, Xun; Mao, Qiang; Zeng, Li; Zheng, Peng; Pu, Juncai; Chen, Jianjun; Wang, Haiyang; Xu, Bing; Zhou, Chanjuan; Xie, Peng
Abstract
Aims: To clarify the role of the gut-brain axis in depression. Main methods: We used the iTRAQ technique to identify differential proteins in the intestine of the rat model of chronic unpredictable mild stress (CUMS)-induced depression. Significant differential proteins were subjected to Gene Ontology (GO) functional annotations and KEGG pathway enrichment analysis. Key proteins were validated at the mRNA and protein levels. The levels of cytokines in the intestine, serum and hypothalamus were examined by ELISA. HPLC-UV was used to detect the levels of amino acids. Key findings: In the rat intestine, 349 differential proteins (209 downregulated, 140 upregulated) were identified. GO analysis indicated that "protein complex assembly" was the first-ranked biological process. SNARE complex components, including SNAP23, VAMP3 and VAMP8, were increased at the mRNA levels, while only VAMP3 and VAMP8 were also upregulated at the protein level. TNF alpha, IL6 and IL1 beta were upregulated in the GUMS rat intestine, while TNF alpha was decreased in the serum and hypothalamus. IL1 beta was decreased in the serum. "Protein digestion and absorption" was the most significantly enriched KEGG pathway, involving 5 differential proteins: SLC9A3, ANPEP, LAT1, ASCT2 and B(0)AT1. Glutamine, glycine and aspartic acid were perturbed in the GUMS rat intestine. Significance: Our findings suggest that GUMS enhances the adaptive immune response in the intestine through ER-phagosome pathway mediated by SNARE complex and disturb absorption of amino acids. It advances our understanding of the role of gut-brain axis in depression and provides a potential therapeutic target for the disease.
Differential Gene Expression Profiling of Mouse Uterine Luminal Epithelium During Periimplantation
REPRODUCTIVE SCIENCES
Authors: Xiao, Shuo; Diao, Honglu; Zhao, Fei; Li, Rong; He, Naya; Ye, Xiaoqin
Abstract
Uterine luminal epithelium (LE) is critical for establishing uterine receptivity. Microarray analysis of gestation day 3.5 (D3.5, preimplantation) and D4.5 (postimplantation) LE from natural pregnant mice identified 382 upregulated and 245 downregulated genes in the D4.5 LE. Gene Ontology annotation grouped 186 upregulated and 103 downregulated genes into 22 and 15 enriched subcategories, respectively, in regulating DNA-dependent transcription, metabolism, cell morphology, ion transport, immune response, apoptosis, signal transduction, and so on. Signaling pathway analysis revealed 99 genes in 21 significantly changed signaling pathways, with 14 of these pathways involved in metabolism. In situ hybridization confirmed the temporal expression of 12 previously uncharacterized genes, including Atp6v0a4, Atp6v0d2, F3, Ggh, Tmprss11d, Tmprss13, Anpep, Fxyd4, Naip5, Npl, Nudt19, and Tpm1 in the periimplantation uterus. This study provides a comprehensive picture of the differentially expressed genes in the periimplantation LE to help understand the molecular mechanism of LE transformation upon establishment of uterine receptivity.