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MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem

Jeongeun Hyun1, Sihyung Wang1, Jieun Kim1

  • 1Department of Integrated Biological Science, Pusan, 609-735, Korea.

Scientific Reports
|September 16, 2015
PubMed

Insights

Chorionic plate-derived mesenchymal stem cells (CP-MSCs) promote liver regeneration by secreting microRNA-125b. This microRNA suppresses Hedgehog (Hh) signaling, reducing fibrosis and aiding liver repair.

Area of Science:

  • Regenerative Medicine
  • Molecular Biology
  • Hepatology

Background:

  • Mesenchymal stem cells (MSCs) from the chorionic plate (CP-MSCs) show potential in promoting liver regeneration.
  • The precise molecular mechanisms, particularly the role of microRNAs and Hedgehog (Hh) signaling, are not fully understood.
  • Hh signaling is crucial for liver tissue reconstruction following injury.

Purpose of the Study:

  • To investigate the hypothesis that microRNAs from CP-MSCs regulate Hh signaling, thereby influencing liver regeneration.
  • To elucidate the role of microRNA-125b in CP-MSC-mediated modulation of Hh signaling and liver fibrosis.
  • To determine the therapeutic potential of CP-MSCs in liver injury models.

Main Methods:

  • Utilized a carbon tetrachloride (CCl4)-induced liver injury rat model transplanted with human CP-MSCs.
  • Analyzed the expression of Sonic Hh (a key Hh ligand) and Hh-target genes in liver tissues.
  • Co-cultured CP-MSCs with human hepatic stellate cells (LX2) and investigated the role of microRNA-125b using inhibitors and exosomes.

Main Results:

  • CP-MSC transplantation significantly decreased Sonic Hh levels and downregulated Hh-target genes in injured livers.
  • Reduced progenitor cell expansion and significant regression of liver fibrosis were observed in CP-MSC treated rats.
  • CP-MSCs, via microRNA-125b within exosomes, suppressed Hh signaling activation and profibrotic gene expression in hepatic stellate cells.

Conclusions:

  • MicroRNA-125b secreted by CP-MSCs plays a critical role in suppressing Hh signaling activation.
  • This microRNA-mediated suppression of Hh signaling contributes to reduced liver fibrosis and promotes liver regeneration.
  • CP-MSCs represent a promising cell-based therapy for liver diseases by modulating microRNA-Hh signaling pathways.

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