Regulation of liver regeneration by microRNAs

• Applicant: Professor Amar Deep Sharma, Ph.D.
• Subject Area: Gastroenterology
• Term: from 2012 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 206120228

Following tissue loss or injury, the liver shows a remarkable capacity to regenerate and restore its original mass. The process requires the interplay of multiple key regulatory circuitries. 19-25 oligonucleotides long non-coding microRNAs have been suggested to regulate proteins necessary for liver regeneration at the posttranscriptional level. We and others have reported differential regulation of microRNAs during liver regeneration. However, to date little is known about the specific role of individual microRNAs in the control of liver regeneration in vivo. In the current proposal, we aim to investigate the in vivo function of microRNAs, identified in our recent work on liver regeneration. We will utilize the high liver tropism of adeno-associated virus (AAV) serotype 8 vectors for in vivo modulation of the miRNAs. Identification of microRNAs, which modulate liver regeneration in vivo, would broaden our basic understanding of importance of microRNAs in liver regeneration at the molecular level. Furthermore, microRNAs that enhance proliferation during liver regeneration may be developed as pharmacological augmenters of proliferation in clinical situations such as acute liver failure, whereas microRNAs that inhibit proliferation may serve as attenuators of liver cancer progression.

• DFG Programme: Research Grants