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Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration
Published on: May 31, 2018
MiR-17~92 ablation impairs liver regeneration in an estrogen-dependent manner
Yongjie Zhou1,2, Lei Zhang1,2, Hongjie Ji1,2
1Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
As one of the most important post-transcriptional regulators, microRNAs (miRNAs) participate in diverse biological processes, including the regulation of cell proliferation. MiR-17~92 has been found to act as an oncogene, and it is closely associated with cell proliferation. However, its role in liver regeneration is still unclear. We generated a hepatocyte-specific miR-17~92-deficient mouse and used a mouse model with 70% partial hepatectomy (PH) or intraperitoneal injection of carbon tetrachloride to demonstrate the role of MiR-17~92 in liver regeneration. In quiescent livers, the expression of the miR-17~92 cluster showed a gender disparity, with much higher expression in female mice. The expression of four members of this cluster was found to be markedly reduced after 70% PH. The ablation of miR-17~92 led to obvious regeneration impairment during the early-stage regeneration in the female mice. Ovariectomy greatly reduced miR-17~92 expression but significantly promoted liver regeneration in wild-type mice. In addition, early regeneration impairment in miR-17~92-deficient livers could be largely restored following ovariectomy. The proliferation suppressors p21 and Pten were found to be the target effectors of miR-17~92. MiR-17~92 disruption resulted in elevated protein levels of p21 and Pten in regenerating livers. MiR-17~92 functions as a proliferation stimulator and acts in an oestrogen-dependent manner. The loss of this miRNA results in increases in p21 and Pten expression and therefore impairs liver regeneration in female mice.
Insights
MicroRNA-17~92 (miR-17~92) stimulates liver regeneration in female mice by suppressing p21 and Pten. Its loss impairs regeneration, an effect reversed by ovariectomy, highlighting estrogen
Area of Science:
- Molecular Biology
- Cell Biology
- Regenerative Medicine
Background:
- MicroRNAs (miRNAs) are key post-transcriptional regulators involved in cell proliferation.
- The miR-17~92 cluster is implicated as an oncogene, but its function in liver regeneration remains elusive.
- Understanding miRNA roles is crucial for advancing regenerative medicine and cancer research.
Purpose of the Study:
- To investigate the role of the miR-17~92 cluster in liver regeneration.
- To determine the influence of gender and estrogen on miR-17~92's function in liver repair.
- To identify the molecular targets mediating miR-17~92's effects on hepatocyte proliferation.
Main Methods:
- Generated hepatocyte-specific miR-17~92-deficient mice.
- Utilized partial hepatectomy and carbon tetrachloride models for liver injury.
- Performed ovariectomy to assess the role of estrogen.
- Analyzed protein levels of proliferation regulators p21 and Pten.
Main Results:
- miR-17~92 expression exhibits gender disparity, higher in females, and decreases post-partial hepatectomy.
- Ablation of miR-17~92 impairs early liver regeneration in female mice.
- Ovariectomy reduces miR-17~92 expression, enhances liver regeneration, and rescues impairment in deficient mice.
- miR-17~92 targets and suppresses the proliferation inhibitors p21 and Pten.
Conclusions:
- miR-17~92 acts as a proliferation stimulator in liver regeneration in an estrogen-dependent manner.
- Loss of miR-17~92 increases p21 and Pten, leading to impaired liver regeneration, particularly in females.
- Estrogen signaling modulates miR-17~92 expression and its impact on liver repair mechanisms.
