Network-based integrated analysis of omics data reveal novel players of TGF-β1-induced EMT in human peritoneal mesothelial cells

• Published in: Scientific reports Vol. 9; no. 1; p. 1497
• Main Authors: Han, Soo Min, Ryu, Hye-Myung, Suh, Jinjoo, Lee, Kong-Joo, Choi, Soon-Youn, Choi, Sangdun, Kim, Yong-Lim, Huh, Joo Young, Ha, Hunjoo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.02.2019; Nature Publishing Group
• Subjects: 13/106; 13/95; 38/39; 38/61; 38/77; 38/89; 631/114/2401; 631/337/2019; 692/4022/1950/1724; 82/1; Data processing; Dialysis; E-cadherin; Extracellular matrix; Fibronectin; Fibrosis; Humanities and Social Sciences; Mesenchyme; multidisciplinary; Oxidative stress; Peritoneal dialysis; Peritoneum; Proteomics; Science; Science (multidisciplinary); Therapeutic applications; Transforming growth factor-b1; Zonula occludens-1 protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-37101-9

Long-term peritoneal dialysis is associated with progressive fibrosis of the peritoneum. Epithelial-mesenchymal transition (EMT) of mesothelial cells is an important mechanism involved in peritoneal fibrosis, and TGF-β1 is considered central in this process. However, targeting currently known TGF-β1-associated pathways has not proven effective to date. Therefore, there are still gaps in understanding the mechanisms underlying TGF-β1-associated EMT and peritoneal fibrosis. We conducted network-based integrated analysis of transcriptomic and proteomic data to systemically characterize the molecular signature of TGF-β1-stimulated human peritoneal mesothelial cells (HPMCs). To increase the power of the data, multiple expression datasets of TGF-β1-stimulated human cells were employed, and extended based on a human functional gene network. Dense network sub-modules enriched with differentially expressed genes by TGF-β1 stimulation were prioritized and genes of interest were selected for functional analysis in HPMCs. Through integrated analysis, ECM constituents and oxidative stress-related genes were shown to be the top-ranked genes as expected. Among top-ranked sub-modules, TNFAIP6 , ZC3H12A , and NNT were validated in HPMCs to be involved in regulation of E-cadherin, ZO-1, fibronectin, and αSMA expression. The present data shows the validity of network-based integrated analysis in discovery of novel players in TGF-β1-induced EMT in peritoneal mesothelial cells, which may serve as new prognostic markers and therapeutic targets for peritoneal dialysis patients.