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

Ting Xiao, Wen Meng, Zhangliu Jin, Jing Wang, Jiangming Deng, Jie Wen, Bilian Liu, Meilian Liu, Juli Bai, Feng Liu

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number771
JournalCommunications Biology
Volume5
Issue number1
DOIs
StatePublished - Dec 2022
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • Medicine (miscellaneous)

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