Network-based integrated analysis of omics data reveal novel players of TGF-β1-induced EMT in human peritoneal mesothelial cells
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...
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| Veröffentlicht in: | Scientific reports 2019-02, Vol.9 (1), p.1497-1497, Article 1497 |
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| description | 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. |
| doi_str_mv | 10.1038/s41598-018-37101-9 |
| format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-37101-9</identifier><identifier>PMID: 30728376</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>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</subject><ispartof>Scientific reports, 2019-02, Vol.9 (1), p.1497-1497, Article 1497</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4559-a0b4a5949c48c7b6a4d0237e6ed8222ae6dc319deccb4102bdd5d362869276e93</citedby><cites>FETCH-LOGICAL-c4559-a0b4a5949c48c7b6a4d0237e6ed8222ae6dc319deccb4102bdd5d362869276e93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365569/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365569/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30728376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Soo Min</creatorcontrib><creatorcontrib>Ryu, Hye-Myung</creatorcontrib><creatorcontrib>Suh, Jinjoo</creatorcontrib><creatorcontrib>Lee, Kong-Joo</creatorcontrib><creatorcontrib>Choi, Soon-Youn</creatorcontrib><creatorcontrib>Choi, Sangdun</creatorcontrib><creatorcontrib>Kim, Yong-Lim</creatorcontrib><creatorcontrib>Huh, Joo Young</creatorcontrib><creatorcontrib>Ha, Hunjoo</creatorcontrib><title>Network-based integrated analysis of omics data reveal novel players of TGF-β1-induced EMT in human peritoneal mesothelial cells</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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.</description><subject>13/106</subject><subject>13/95</subject><subject>38/39</subject><subject>38/61</subject><subject>38/77</subject><subject>38/89</subject><subject>631/114/2401</subject><subject>631/337/2019</subject><subject>692/4022/1950/1724</subject><subject>82/1</subject><subject>Data processing</subject><subject>Dialysis</subject><subject>E-cadherin</subject><subject>Extracellular matrix</subject><subject>Fibronectin</subject><subject>Fibrosis</subject><subject>Humanities and Social Sciences</subject><subject>Mesenchyme</subject><subject>multidisciplinary</subject><subject>Oxidative stress</subject><subject>Peritoneal dialysis</subject><subject>Peritoneum</subject><subject>Proteomics</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Therapeutic applications</subject><subject>Transforming growth factor-b1</subject><subject>Zonula occludens-1 protein</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1uFDEQhVsIRKKQC7BALbFhY_C_2xskFCUBKcBmWFtuu2bGodse7O6JZsmVOAhnwpMJIbDAG5dUXz2_8mua5wS_Jph1bwonQncIkw4xRTBB-lFzTDEXiDJKHz-oj5rTUq5xPYJqTvTT5ohhRTum5HHz_RNMNyl_Rb0t4NsQJ1hlO9XSRjvsSihtWrZpDK603k62zbAFO7QxbWFoN4PdQb5FFpcX6OcPgkL0s6vj5x8XVa1dz6ON7QZymFLcD45Q0rSGIdTawTCUZ82TpR0KnN7dJ82Xi_PF2Xt09fnyw9m7K-S4EBpZ3HMrNNeOd0710nKPKVMgwXeUUgvSO0a0B-d6TjDtvReeSdpJTZUEzU6atwfdzdyP4B3EKdvBbHIYbd6ZZIP5uxPD2qzS1kgmhZB7gVd3Ajl9m6FMZgxlv4KNkOZiqguNFVdaVfTlP-h1mnP90EoRJRXWQpNK0QPlciolw_LeDMFmH7I5hGxqyOY2ZLN38eLhGvcjvyOtADsApbbiCvKft_8j-wvrwLSV</recordid><startdate>20190206</startdate><enddate>20190206</enddate><creator>Han, Soo Min</creator><creator>Ryu, Hye-Myung</creator><creator>Suh, Jinjoo</creator><creator>Lee, Kong-Joo</creator><creator>Choi, Soon-Youn</creator><creator>Choi, Sangdun</creator><creator>Kim, Yong-Lim</creator><creator>Huh, Joo Young</creator><creator>Ha, Hunjoo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190206</creationdate><title>Network-based integrated analysis of omics data reveal novel players of TGF-β1-induced EMT in human peritoneal mesothelial cells</title><author>Han, Soo Min ; 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30728376</pmid><doi>10.1038/s41598-018-37101-9</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Network-based integrated analysis of omics data reveal novel players of TGF-β1-induced EMT in human peritoneal mesothelial cells |
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