MicroRNA-125b-5p Regulates Hepatocyte Proliferation During the Termination Phase of Liver Regeneration.
dc.contributor.author | Yang, Dakai | |
dc.contributor.author | Dai, Zhen | |
dc.contributor.author | Yang, Taihua | |
dc.contributor.author | Balakrishnan, Asha | |
dc.contributor.author | Yuan, Qinggong | |
dc.contributor.author | Vondran, Florian W R | |
dc.contributor.author | Manns, Michael P | |
dc.contributor.author | Ott, Michael | |
dc.contributor.author | Cantz, Tobias | |
dc.contributor.author | Sharma, Amar Deep | |
dc.date.accessioned | 2021-09-16T13:09:25Z | |
dc.date.available | 2021-09-16T13:09:25Z | |
dc.date.issued | 2020-09-15 | |
dc.identifier.citation | Hepatol Commun. 2020 Sep 15;4(12):1851-1863. doi: 10.1002/hep4.1597. | en_US |
dc.identifier.pmid | 33305155 | |
dc.identifier.doi | 10.1002/hep4.1597 | |
dc.identifier.uri | http://hdl.handle.net/10033/623035 | |
dc.description.abstract | The ability of the liver to regenerate and restore mass limits the increasing mortality rate due to life-threatening liver diseases. Successful liver regeneration is accomplished in multiple stages, of which the priming and proliferation phases are well studied. However, the regulatory pathways, specifically microRNA (miRNA)-mediated posttranscriptional regulation, which prevent uncontrolled proliferation and mediate the termination of liver regeneration, are not well understood. We identified differentially regulated miRNAs during the termination phase after 2/3 partial hepatectomy (PH) in mice, which is a well-established mouse model of liver regeneration. We further evaluated the function of differentially regulated miRNAs in primary mouse hepatocytes by using mimics and inhibitors and in vivo by using adeno-associated virus (AAV) serotype 8. A candidate miRNA target was identified by messenger RNA array in silico analyses and validated in primary mouse and human hepatocytes. Using miRNA profiling, we discovered miR-125b-5p as a novel regulator of hepatocyte proliferation in the late phase of liver regeneration. AAV-mediated miR-125b-5p delivery in mice enhanced the endogenous regenerative capacity and resulted in improved restoration of liver mass after 2/3 PH. Further, we found that ankyrin repeat and BTB/POZ domain containing protein 1 (Abtb1) is a direct target of miR-125b-5p in primary mouse and human hepatocytes and contributes to the pro-proliferative activity of miR-125b-5p by forkhead box G1 (FOXG1) and the cyclin-dependent kinase inhibitor 1A (p21) pathway. Conclusion: miR-125b-5p has an important role in regulating hepatocyte proliferation in the termination phase of liver regeneration and may serve as a potential therapeutic target in various liver diseases that often exhibit deregulated hepatocyte proliferation. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | MicroRNA-125b-5p Regulates Hepatocyte Proliferation During the Termination Phase of Liver Regeneration. | en_US |
dc.type | Article | en_US |
dc.identifier.eissn | 2471-254X | |
dc.contributor.department | TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany. | en_US |
dc.identifier.journal | Hepatology communications | en_US |
dc.source.volume | 4 | |
dc.source.issue | 12 | |
dc.source.beginpage | 1851 | |
dc.source.endpage | 1863 | |
refterms.dateFOA | 2021-09-16T13:09:26Z | |
dc.source.journaltitle | Hepatology communications | |
dc.source.country | United States |