Combined analysis of metabolomes, proteomes, and transcriptomes of Hepatitis C Virus-infected cells and liver to identify pathways associated with disease development
Background & Aims - The mechanisms of hepatitis C virus (HCV) infection, liver disease progression, and hepatocarcinogenesis are only partially understood. We performed genomic, proteomic, and metabolomic analyses of HCV-infected cells and chimeric mice to learn more about these processes. - Met...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2019
|
| In: |
Gastroenterology
Year: 2019, Jahrgang: 157, Heft: 2, Pages: 537-551.e9 |
| ISSN: | 1528-0012 |
| DOI: | 10.1053/j.gastro.2019.04.003 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1053/j.gastro.2019.04.003 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0016508519356707 
|
| Verfasserangaben: | Joachim Lupberger, Tom Croonenborghs, Armando Andres Roca Suarez, Nicolaas Van Renne, Frank Jühling, Marine A. Oudot, Alessia Virzì, Simonetta Bandiera, Carole Jamey, Gergö Meszaros, Daniel Brumaru, Atish Mukherji, Sarah C. Durand, Laura Heydmann, Eloi R. Verrier, Hussein El Saghire, Nourdine Hamdane, Ralf Bartenschlager, Shaunt Fereshetian, Evelyn Ramberger, Rileen Sinha, Mohsen Nabian, Celine Everaert, Marko Jovanovic, Philipp Mertins, Steven A. Carr, Kazuaki Chayama, Nassim Dali-Youcef, Romeo Ricci, Nabeel M. Bardeesy, Naoto Fujiwara, Olivier Gevaert, Mirjam B. Zeisel, Yujin Hoshida, Nathalie Pochet, and Thomas F. Baumert |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1689538376 | ||
| 003 | DE-627 | ||
| 005 | 20230427063104.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200206s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1053/j.gastro.2019.04.003 |2 doi | |
| 035 | |a (DE-627)1689538376 | ||
| 035 | |a (DE-599)KXP1689538376 | ||
| 035 | |a (OCoLC)1341304012 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Lupberger, Joachim |d 1974- |e VerfasserIn |0 (DE-588)133552853 |0 (DE-627)548188513 |0 (DE-576)29992680X |4 aut | |
| 245 | 1 | 0 | |a Combined analysis of metabolomes, proteomes, and transcriptomes of Hepatitis C Virus-infected cells and liver to identify pathways associated with disease development |c Joachim Lupberger, Tom Croonenborghs, Armando Andres Roca Suarez, Nicolaas Van Renne, Frank Jühling, Marine A. Oudot, Alessia Virzì, Simonetta Bandiera, Carole Jamey, Gergö Meszaros, Daniel Brumaru, Atish Mukherji, Sarah C. Durand, Laura Heydmann, Eloi R. Verrier, Hussein El Saghire, Nourdine Hamdane, Ralf Bartenschlager, Shaunt Fereshetian, Evelyn Ramberger, Rileen Sinha, Mohsen Nabian, Celine Everaert, Marko Jovanovic, Philipp Mertins, Steven A. Carr, Kazuaki Chayama, Nassim Dali-Youcef, Romeo Ricci, Nabeel M. Bardeesy, Naoto Fujiwara, Olivier Gevaert, Mirjam B. Zeisel, Yujin Hoshida, Nathalie Pochet, and Thomas F. Baumert |
| 264 | 1 | |c 2019 | |
| 300 | |a 24 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 06.02.2020 | ||
| 500 | |a Received 3 August 2018 | ||
| 520 | |a Background & Aims - The mechanisms of hepatitis C virus (HCV) infection, liver disease progression, and hepatocarcinogenesis are only partially understood. We performed genomic, proteomic, and metabolomic analyses of HCV-infected cells and chimeric mice to learn more about these processes. - Methods - Huh7.5.1dif (hepatocyte-like cells) were infected with culture-derived HCV and used in RNA sequencing, proteomic, metabolomic, and integrative genomic analyses. uPA/SCID (urokinase-type plasminogen activator/severe combined immunodeficiency) mice were injected with serum from HCV-infected patients; 8 weeks later, liver tissues were collected and analyzed by RNA sequencing and proteomics. Using differential expression, gene set enrichment analyses, and protein interaction mapping, we identified pathways that changed in response to HCV infection. We validated our findings in studies of liver tissues from 216 patients with HCV infection and early-stage cirrhosis and paired biopsy specimens from 99 patients with hepatocellular carcinoma, including 17 patients with histologic features of steatohepatitis. Cirrhotic liver tissues from patients with HCV infection were classified into 2 groups based on relative peroxisome function; outcomes assessed included Child-Pugh class, development of hepatocellular carcinoma, survival, and steatohepatitis. Hepatocellular carcinomas were classified according to steatohepatitis; the outcome was relative peroxisomal function. - Results - We quantified 21,950 messenger RNAs (mRNAs) and 8297 proteins in HCV-infected cells. Upon HCV infection of hepatocyte-like cells and chimeric mice, we observed significant changes in levels of mRNAs and proteins involved in metabolism and hepatocarcinogenesis. HCV infection of hepatocyte-like cells significantly increased levels of the mRNAs, but not proteins, that regulate the innate immune response; we believe this was due to the inhibition of translation in these cells. HCV infection of hepatocyte-like cells increased glucose consumption and metabolism and the STAT3 signaling pathway and reduced peroxisome function. Peroxisomes mediate β-oxidation of very long-chain fatty acids; we found intracellular accumulation of very long-chain fatty acids in HCV-infected cells, which is also observed in patients with fatty liver disease. Cells in livers from HCV-infected mice had significant reductions in levels of the mRNAs and proteins associated with peroxisome function, indicating perturbation of peroxisomes. We found that defects in peroxisome function were associated with outcomes and features of HCV-associated cirrhosis, fatty liver disease, and hepatocellular carcinoma in patients. - Conclusions - We performed combined transcriptome, proteome, and metabolome analyses of liver tissues from HCV-infected hepatocyte-like cells and HCV-infected mice. We found that HCV infection increases glucose metabolism and the STAT3 signaling pathway and thereby reduces peroxisome function; alterations in the expression levels of peroxisome genes were associated with outcomes of patients with liver diseases. These findings provide insights into liver disease pathogenesis and might be used to identify new therapeutic targets. | ||
| 650 | 4 | |a HCC | |
| 650 | 4 | |a immune regulation | |
| 650 | 4 | |a metabolic disease | |
| 650 | 4 | |a signal transduction | |
| 700 | 1 | |a Croonenborghs, Tom |e VerfasserIn |4 aut | |
| 700 | 1 | |a Roca Suarez, Armando Andres |e VerfasserIn |4 aut | |
| 700 | 1 | |a Van Renne, Nicolaas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jühling, Frank |e VerfasserIn |4 aut | |
| 700 | 1 | |a Oudot, Marine A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Virzì, Alessia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bandiera, Simonetta |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jamey, Carole |e VerfasserIn |4 aut | |
| 700 | 1 | |a Meszaros, Gergö |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brumaru, Daniel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mukherji, Atish |e VerfasserIn |4 aut | |
| 700 | 1 | |a Durand, Sarah C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Heydmann, Laura |e VerfasserIn |4 aut | |
| 700 | 1 | |a Verrier, Eloi R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a El Saghire, Hussein |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hamdane, Nourdine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bartenschlager, Ralf |d 1958- |e VerfasserIn |0 (DE-588)1058097989 |0 (DE-627)796390509 |0 (DE-576)168706067 |4 aut | |
| 700 | 1 | |a Fereshetian, Shaunt |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ramberger, Evelyn |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sinha, Rileen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nabian, Mohsen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Everaert, Celine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jovanovic, Marko |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mertins, Philipp |e VerfasserIn |4 aut | |
| 700 | 1 | |a Carr, Steven A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chayama, Kazuaki |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dali-Youcef, Nassim |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ricci, Romeo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bardeesy, Nabeel M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fujiwara, Naoto |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gevaert, Olivier |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zeisel, Mirjam B. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hoshida, Yujin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pochet, Nathalie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Baumert, Thomas |e VerfasserIn |0 (DE-588)108844038X |0 (DE-627)849543568 |0 (DE-576)45919058X |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Gastroenterology |d New York, NY : Elsevier, 1949 |g 157(2019), 2, Seite 537-551.e9 |h Online-Ressource |w (DE-627)270937293 |w (DE-600)1478699-0 |w (DE-576)078590221 |x 1528-0012 |7 nnas |a Combined analysis of metabolomes, proteomes, and transcriptomes of Hepatitis C Virus-infected cells and liver to identify pathways associated with disease development |
| 773 | 1 | 8 | |g volume:157 |g year:2019 |g number:2 |g pages:537-551.e9 |g extent:24 |a Combined analysis of metabolomes, proteomes, and transcriptomes of Hepatitis C Virus-infected cells and liver to identify pathways associated with disease development |
| 856 | 4 | 0 | |u https://doi.org/10.1053/j.gastro.2019.04.003 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S0016508519356707 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200206 | ||
| 993 | |a Article | ||
| 994 | |a 2019 | ||
| 998 | |g 1058097989 |a Bartenschlager, Ralf |m 1058097989:Bartenschlager, Ralf |d 910000 |d 911700 |e 910000PB1058097989 |e 911700PB1058097989 |k 0/910000/ |k 1/910000/911700/ |p 18 | ||
| 999 | |a KXP-PPN1689538376 |e 3588595317 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"recId":"1689538376","title":[{"title_sort":"Combined analysis of metabolomes, proteomes, and transcriptomes of Hepatitis C Virus-infected cells and liver to identify pathways associated with disease development","title":"Combined analysis of metabolomes, proteomes, and transcriptomes of Hepatitis C Virus-infected cells and liver to identify pathways associated with disease development"}],"name":{"displayForm":["Joachim Lupberger, Tom Croonenborghs, Armando Andres Roca Suarez, Nicolaas Van Renne, Frank Jühling, Marine A. Oudot, Alessia Virzì, Simonetta Bandiera, Carole Jamey, Gergö Meszaros, Daniel Brumaru, Atish Mukherji, Sarah C. Durand, Laura Heydmann, Eloi R. Verrier, Hussein El Saghire, Nourdine Hamdane, Ralf Bartenschlager, Shaunt Fereshetian, Evelyn Ramberger, Rileen Sinha, Mohsen Nabian, Celine Everaert, Marko Jovanovic, Philipp Mertins, Steven A. Carr, Kazuaki Chayama, Nassim Dali-Youcef, Romeo Ricci, Nabeel M. Bardeesy, Naoto Fujiwara, Olivier Gevaert, Mirjam B. Zeisel, Yujin Hoshida, Nathalie Pochet, and Thomas F. Baumert"]},"language":["eng"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"physDesc":[{"extent":"24 S."}],"note":["Gesehen am 06.02.2020","Received 3 August 2018"],"person":[{"roleDisplay":"VerfasserIn","family":"Lupberger","given":"Joachim","role":"aut","display":"Lupberger, Joachim"},{"family":"Croonenborghs","roleDisplay":"VerfasserIn","role":"aut","display":"Croonenborghs, Tom","given":"Tom"},{"roleDisplay":"VerfasserIn","family":"Roca Suarez","display":"Roca Suarez, Armando Andres","role":"aut","given":"Armando Andres"},{"given":"Nicolaas","role":"aut","display":"Van Renne, Nicolaas","family":"Van Renne","roleDisplay":"VerfasserIn"},{"family":"Jühling","roleDisplay":"VerfasserIn","role":"aut","display":"Jühling, Frank","given":"Frank"},{"family":"Oudot","roleDisplay":"VerfasserIn","display":"Oudot, Marine A.","role":"aut","given":"Marine A."},{"roleDisplay":"VerfasserIn","family":"Virzì","role":"aut","display":"Virzì, Alessia","given":"Alessia"},{"display":"Bandiera, Simonetta","role":"aut","given":"Simonetta","roleDisplay":"VerfasserIn","family":"Bandiera"},{"family":"Jamey","roleDisplay":"VerfasserIn","role":"aut","display":"Jamey, Carole","given":"Carole"},{"role":"aut","display":"Meszaros, Gergö","given":"Gergö","roleDisplay":"VerfasserIn","family":"Meszaros"},{"display":"Brumaru, Daniel","role":"aut","given":"Daniel","roleDisplay":"VerfasserIn","family":"Brumaru"},{"given":"Atish","role":"aut","display":"Mukherji, Atish","family":"Mukherji","roleDisplay":"VerfasserIn"},{"given":"Sarah C.","role":"aut","display":"Durand, Sarah C.","roleDisplay":"VerfasserIn","family":"Durand"},{"role":"aut","display":"Heydmann, Laura","given":"Laura","roleDisplay":"VerfasserIn","family":"Heydmann"},{"given":"Eloi R.","display":"Verrier, Eloi R.","role":"aut","roleDisplay":"VerfasserIn","family":"Verrier"},{"display":"El Saghire, Hussein","role":"aut","given":"Hussein","roleDisplay":"VerfasserIn","family":"El Saghire"},{"given":"Nourdine","role":"aut","display":"Hamdane, Nourdine","family":"Hamdane","roleDisplay":"VerfasserIn"},{"role":"aut","display":"Bartenschlager, Ralf","given":"Ralf","roleDisplay":"VerfasserIn","family":"Bartenschlager"},{"family":"Fereshetian","roleDisplay":"VerfasserIn","display":"Fereshetian, Shaunt","role":"aut","given":"Shaunt"},{"family":"Ramberger","roleDisplay":"VerfasserIn","display":"Ramberger, Evelyn","role":"aut","given":"Evelyn"},{"display":"Sinha, Rileen","role":"aut","given":"Rileen","family":"Sinha","roleDisplay":"VerfasserIn"},{"family":"Nabian","roleDisplay":"VerfasserIn","given":"Mohsen","role":"aut","display":"Nabian, Mohsen"},{"roleDisplay":"VerfasserIn","family":"Everaert","given":"Celine","role":"aut","display":"Everaert, Celine"},{"family":"Jovanovic","roleDisplay":"VerfasserIn","given":"Marko","display":"Jovanovic, Marko","role":"aut"},{"role":"aut","display":"Mertins, Philipp","given":"Philipp","family":"Mertins","roleDisplay":"VerfasserIn"},{"given":"Steven A.","display":"Carr, Steven A.","role":"aut","family":"Carr","roleDisplay":"VerfasserIn"},{"given":"Kazuaki","role":"aut","display":"Chayama, Kazuaki","roleDisplay":"VerfasserIn","family":"Chayama"},{"family":"Dali-Youcef","roleDisplay":"VerfasserIn","role":"aut","display":"Dali-Youcef, Nassim","given":"Nassim"},{"role":"aut","display":"Ricci, Romeo","given":"Romeo","roleDisplay":"VerfasserIn","family":"Ricci"},{"display":"Bardeesy, Nabeel M.","role":"aut","given":"Nabeel M.","roleDisplay":"VerfasserIn","family":"Bardeesy"},{"role":"aut","display":"Fujiwara, Naoto","given":"Naoto","roleDisplay":"VerfasserIn","family":"Fujiwara"},{"role":"aut","display":"Gevaert, Olivier","given":"Olivier","roleDisplay":"VerfasserIn","family":"Gevaert"},{"family":"Zeisel","roleDisplay":"VerfasserIn","role":"aut","display":"Zeisel, Mirjam B.","given":"Mirjam B."},{"given":"Yujin","role":"aut","display":"Hoshida, Yujin","family":"Hoshida","roleDisplay":"VerfasserIn"},{"family":"Pochet","roleDisplay":"VerfasserIn","role":"aut","display":"Pochet, Nathalie","given":"Nathalie"},{"given":"Thomas","role":"aut","display":"Baumert, Thomas","family":"Baumert","roleDisplay":"VerfasserIn"}],"origin":[{"dateIssuedKey":"2019","dateIssuedDisp":"2019"}],"relHost":[{"part":{"pages":"537-551.e9","text":"157(2019), 2, Seite 537-551.e9","year":"2019","volume":"157","issue":"2","extent":"24"},"pubHistory":["Nachgewiesen 12.1949 -"],"type":{"media":"Online-Ressource","bibl":"periodical"},"corporate":[{"roleDisplay":"Herausgebendes Organ","role":"isb","display":"American Gastroenterological Association"}],"language":["eng"],"recId":"270937293","disp":"Combined analysis of metabolomes, proteomes, and transcriptomes of Hepatitis C Virus-infected cells and liver to identify pathways associated with disease developmentGastroenterology","title":[{"title":"Gastroenterology","subtitle":"official publication of the American Gastroenterological Association","title_sort":"Gastroenterology"}],"origin":[{"dateIssuedDisp":"1949-","dateIssuedKey":"1949","publisher":"Elsevier ; Williams & Wilkins ; Saunders","publisherPlace":"New York, NY ; Baltimore, Md. ; Philadelphia, Pa. [u.a.]"}],"id":{"zdb":["1478699-0"],"eki":["270937293"],"issn":["1528-0012"]},"physDesc":[{"extent":"Online-Ressource"}],"note":["Gesehen am 21.07.25"]}],"id":{"eki":["1689538376"],"doi":["10.1053/j.gastro.2019.04.003"]}} | ||
| SRT | |a LUPBERGERJCOMBINEDAN2019 | ||