Identification of the C-Reactive Protein Interaction Network Using a Bioinformatics Approach Provides Insights into the Molecular Pathogenesis of Hepatocellular Carcinoma
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Authors: She, Sha; Jiang, Lingyu; Zhang, Zhenfang; Yang, Min; Hu, Huaidong; Hu, Peng; Liao, Yong; Yang, Yixuan; Ren, Hong
Abstract
Background/Aims: C reactive protein (CRP) levels are elevated in many diseases, including malignant tumors and cardiovascular disorders. In this study, the protein interaction network for CRP was evaluated to determine the importance of CRP and its interacting proteins in the molecular pathogenesis of hepatocellular carcinoma (HCC). Methods: Isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometry were used to identify CRP interacting proteins in SMMC7721 cells. Moreover, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to evaluate enriched genes and pathways for differentially expressed genes using DAVID and WebGestalt. Co-immunoprecipitation and western blot analyses were employed to assess interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. Results: In total, 52 proteins that interact with CRP were identified. A GO analysis suggested that most of the interacting proteins were involved in CRP complexes and regulated metabolic processes. A KEGG pathway analysis suggested that most CRP-interacting proteins contribute to the TRAIL signaling pathway, Class I PI3K/Akt signaling pathway, plasma membrane estrogen receptor signaling, Nectin adhesion pathway, and S1P1 pathway. Immunoprecipitation and western blot analyses revealed interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. Conclusions: iTRAQ based proteomic profiling revealed the network of CRP interacting proteins. This network may activate the PI3K/Akt signaling pathway, thereby contributing to the pathogenesis of HCC. (c) 2018 The Author(s) Published by S. Karger AG, Basel
Analysis of underlying genes and functions associated with diabetic kidney disease
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
Authors: Ma, Fuzhe; Sun, Tao; Wu, Meiyan; Wang, Wanning; Xu, Zhonggao
Abstract
This study aimed to investigate the pathogenic characteristics of diabetic kidney disease (DKD) from gene level. The microarray data of GSE30528 and GSE30529 were downloaded to screen the differentially expressed genes (DEGs): (a) DKD glomeruli vs. normal glomeruli; (b) DKD tubuli vs. normal tubuli; (c) normal glomeruli vs. normal tubuli. Then functional enrichment analysis and interaction network analysis of the DEGs were performed. Co-expression network analysis was carried out to study the module preservation. Total 511, 503 and 941 DEGs were identified in groups a, b and c respectively. Functional enrichment analyses found that DEGs in DKD glomeruli were mainly enriched in functions related to actin cytoskeleton; in DKD tubuli were mainly enriched in immune and inflammatory response-associated functions. In the interaction networks constructed by DEGs of DKD glomeruli and DKD tubuli, FYN, FN1, RB1 and CASP3 had higher degrees. Co-expression network analysis revealed 43 modules that did not reach the threshold requirements of preservation in DKD glomeruli. The probes in 43 modules had 44 common probes with differentially expressed probes in DKD glomeruli and DKD tubuli, which were enriched in extracellular matrix-associated terms. In the interaction networks of 43 common probes, FN1, ANXA2, and EFNB2 had higher degrees. The present study indicates that the function terms like actin cytoskeleton, immune and inflammatory response and extracellular matrix may play an important role in the pathogenesis of DKD. Genes such as FN1, EFNB2 and ANXA2 may be used as novel biomarkers in DKD.