| First Author | Oya Y | Year | 2017 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 312 |
| Issue | 5 | Pages | G464-G473 |
| PubMed ID | 28232457 | Mgi Jnum | J:251410 |
| Mgi Id | MGI:6101337 | Doi | 10.1152/ajpgi.00383.2016 |
| Citation | Oya Y, et al. (2017) Dicer-dependent production of microRNA221 in hepatocytes inhibits p27 and is required for liver regeneration in mice. Am J Physiol Gastrointest Liver Physiol 312(5):G464-G473 |
| abstractText | Dicer processes microRNAs (miRs) into active forms in a wide variety of tissues, including the liver. To determine the role of Dicer in liver regeneration, we performed a series of in vivo and in vitro studies in a murine 2/3 hepatectomy model. Dicer was downregulated after 2/3 hepatectomy, and loss of Dicer inhibited liver regeneration associated with decreased cyclin A2 and miR-221, as well as increased levels of the cell cycle inhibitor p27. In vitro, miR-221 inhibited p27 production in primary hepatocytes and increased hepatocyte proliferation. Specific reconstitution of miR-221 in hepatocyte-specific Dicer-null mice inhibited p27 and restored liver regeneration. In wild type mice, targeted inhibition of miR-221 using a cholesterol-conjugated miR-221 inhibited hepatocyte proliferation after 2/3 hepatectomy. These results identify Dicer production of miR-221 as an essential component of a miRNA-dependent mechanism for suppression of p27 that controls the rate of hepatocyte proliferation after partial hepatectomy.NEW & NOTEWORTHY Our findings demonstrate a direct role for microRNAs in controlling the rate of liver regeneration after injury. By deleting Dicer, an enzyme responsible for processing microRNAs into mature forms, we determined miR-221 is a critical microRNA in the physiological process of restoration of liver mass after injury. miR-221 suppresses p27, releasing its inhibitory effects on hepatocyte proliferation. Pharmaceuticals based on miR-221 may be useful to modulate hepatocyte proliferation in the setting of liver injury. |
