miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration

Hepatic miR-182-5p is identified as a key regulator of liver regeneration by stimulating Cyp7a1-mediated cholic acid production in hepatocytes and activating hedgehog (Hh) signaling, consequently increasing cell proliferation. A unique feature of the liver is its high regenerative capacity, which is essential to maintain liver homeostasis. However, key regulators of liver regeneration (LR) remain ill-defined. Here, we identify hepatic miR-182-5p as a key regulator of LR. Suppressing miR-182-5p, whose expression is significantly induced in the liver of mice post two-thirds partial hepatectomy (PH), abrogates PH-induced LR in mice. In contrast, liver-specific overexpression of miR-182-5p promotes LR in mice with PH. Overexpression of miR-182-5p failed to promote proliferation in hepatocytes, but stimulates proliferation when hepatocytes are cocultured with stellate cells. Mechanistically, miR-182-5p stimulates Cyp7a1-mediated cholic acid production in hepatocytes, which promotes hedgehog (Hh) ligand production in stellate cells, leading to the activation of Hh signaling in hepatocytes and consequent cell proliferation. Collectively, our study identified miR-182-5p as a critical regulator of LR and uncovers a Cyp7a1/cholic acid-dependent mechanism by which hepatocytes crosstalk to stellate cells to facilitate LR.

Automated summary

Hepatic miR-182-5p is identified as a key regulator of liver regeneration by promoting Cyp7a1-mediated cholic acid production and activating Hh signaling to stimulate cell proliferation. This study uncovers the critical mechanism of liver regeneration and identifies miR-182-5p as an important factor in the process.