dc.contributor.author |
Csák, Tímea |
|
dc.contributor.author |
Bala S |
|
dc.contributor.author |
Lippai, Dóra |
|
dc.contributor.author |
Kodys K |
|
dc.contributor.author |
Catalano D |
|
dc.contributor.author |
Iracheta-Vellve A |
|
dc.contributor.author |
Szabo G |
|
dc.date.accessioned |
2018-09-17T06:18:06Z |
|
dc.date.available |
2018-09-17T06:18:06Z |
|
dc.date.issued |
2015 |
|
dc.identifier |
84934980367 |
|
dc.identifier.citation |
pagination=e0129251, pages: 21;
journalVolume=10;
journalIssueNumber=6;
journalTitle=PLOS ONE; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/5973 |
|
dc.identifier.uri |
doi:10.1371/journal.pone.0129251 |
|
dc.description.abstract |
BACKGROUND & AIM: MicroRNAs (miRs) regulate hepatic steatosis, inflammation and fibrosis. Fibrosis is the consequence of chronic tissue damage and inflammation. We hypothesized that deficiency of miR-155, a master regulator of inflammation, attenuates steatohepatitis and fibrosis. METHODS: Wild type (WT) and miR-155-deficient (KO) mice were fed methionine-choline-deficient (MCD) or -supplemented (MCS) control diet for 5 weeks. Liver injury, inflammation, steatosis and fibrosis were assessed. RESULTS: MCD diet resulted in steatohepatitis and increased miR-155 expression in total liver, hepatocytes and Kupffer cells. Steatosis and expression of genes involved in fatty acid metabolism were attenuated in miR-155 KO mice after MCD feeding. In contrast, miR-155 deficiency failed to attenuate inflammatory cell infiltration, nuclear factor kappa beta (NF-kappaB) activation and enhanced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and monocyte chemoattractant protein-1 (MCP1) in MCD diet-fed mice. We found a significant attenuation of apoptosis (cleaved caspase-3) and reduction in collagen and alpha smooth muscle actin (alphaSMA) levels in miR-155 KO mice compared to WTs on MCD diet. In addition, we found attenuation of platelet derived growth factor (PDGF), a pro-fibrotic cytokine; SMAD family member 3 (Smad3), a protein involved in transforming growth factor-beta (TGFbeta) signal transduction and vimentin, a mesenchymal marker and indirect indicator of epithelial-to-mesenchymal transition (EMT) in miR-155 KO mice. Nuclear binding of CCAAT enhancer binding protein beta (C/EBPbeta) a miR-155 target involved in EMT was significantly increased in miR-155 KO compared to WT mice. CONCLUSIONS: Our novel data demonstrate that miR-155 deficiency can reduce steatosis and fibrosis without decreasing inflammation in steatohepatitis. |
|
dc.relation.ispartof |
urn:issn:1932-6203 |
|
dc.title |
MicroRNA-155 Deficiency Attenuates Liver Steatosis and Fibrosis without Reducing Inflammation in a Mouse Model of Steatohepatitis |
|
dc.type |
Journal Article |
|
dc.date.updated |
2018-07-20T07:00:37Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
2976219 |
|
dc.identifier.wos |
000355701600094 |
|
dc.identifier.pubmed |
26042593 |
|
dc.contributor.department |
SE/AOK/K/II. Sz. Belgyógyászati Klinika |
|
dc.contributor.institution |
Semmelweis Egyetem |
|
dc.mtmt.swordnote |
Csak T and Bala S contributed equally to this work. |
|