Network-based integrated analysis of omics data reveal novel players ofTGF-beta 1-induced EMT in human peritoneal mesothelial cells
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Han, Soo Min; Suh, Jinjoo; Lee, Kong-Joo; Ha, Hunjoo] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul, South Korea; [Han, Soo Min] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul, South Korea; [Ryu, Hye-Myung; Choi, Soon-Youn; Kim, Yong-Lim] Kyungpook Natl Univ, Sch Med, Dept Internal Med, Seoul, South Korea; [Choi, Sangdun] Ajou Univ, Dept Mol Sci & Technol, Suwon, South Korea; [Huh, Joo Young] Chonnam Natl Univ, Coll Pharm, Gwangju, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159940
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s41598-018-37101-9
- PubMed https://pubmed.ncbi.nlm.nih.gov/30728376
초록/요약
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-beta 1 is considered central in this process. However, targeting currently known TGF-beta 1-associated pathways has not proven effective to date. Therefore, there are still gaps in understanding the mechanisms underlying TGF-beta 1-associated EMT and peritoneal fibrosis. We conducted network-based integrated analysis of transcriptomic and proteomic data to systemically characterize the molecular signature ofTGF-beta 1-stimulated human peritoneal mesothelial cells (HPMCs). To increase the power of the data, multiple expression datasets ofTGF-beta 1-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-beta 1 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 NNTwere validated in HPMCs to be involved in regulation of E-cadherin, ZO-1, fibronectin, and alpha SMA expression. The present data shows the validity of network-based integrated analysis in discovery of novel players in TGF-beta 1-induced EMT in peritoneal mesothelial cells, which may serve as new prognostic markers and therapeutic targets for peritoneal dialysis patients.
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