title: MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem cells.
abstract: Although chorionic plate-derived mesenchymal stem cells (CP-MSCs) were shown to promote liver regeneration, the mechanisms underlying the effect remain unclear. Hedgehog (Hh) signaling orchestrates tissue reconstruction in damaged liver. MSCs release microRNAs mediating various cellular responses. Hence, we hypothesized that microRNAs from CP-MSCs regulated Hh signaling, which influenced liver regeneration. Livers were obtained from carbon tetrachloride (CCl4)-treated rats transplanted with human CP-MSCs (Tx) or saline (non-Tx). Sonic Hh, one of Hh ligands, increased in CCl4-treated liver, whereas it decreased in CP-MSC-treated liver with CCl4. The expression of Hh-target genes was significantly downregulated in the Tx. Reduced expansion of progenitors and regressed fibrosis were observed in the liver of the Tx rats. CP-MSCs suppressed the expression of Hh and profibrotic genes in co-cultured LX2 (human hepatic stellate cell) with CP-MSCs. MicroRNA-125b targeting smo was retained in exosomes of CP-MSCs. CP-MSCs with microRNA-125b inhibitor failed to attenuate the expression of Hh signaling and profibrotic genes in the activated HSCs. Therefore, these results demonstrated that microRNA-125b from CP-MSCs suppressed the activation of Hh signaling, which promoted the reduced fibrosis, suggesting that microRNA-mediated regulation of Hh signaling contributed to liver regeneration by CP-MSCs.
authors.affiliation: Department of Integrated Biological Science, Pusan, 609-735, Korea.
authors.forename: Jeongeun
authors.initials: J
authors.lastname: Hyun
authors.affiliation: Department of Integrated Biological Science, Pusan, 609-735, Korea.
authors.forename: Sihyung
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Integrated Biological Science, Pusan, 609-735, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam, 463-400, Korea.
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
authors.affiliation: Department of Integrated Biological Science, Pusan, 609-735, Korea.|Department of Biological Sciences, College of Natural Science, Pusan National University, Pusan, 609-735, Korea.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Jung
mesh_terms: D000818:Animals; D002460:Cell Line; D002823:Chorion / Q000166:cytology*; D015536:Down-Regulation; D005355:Fibrosis; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D015398:Signal Transduction; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: C546742:GLI3 protein, rat; D053823:Hedgehog Proteins; C550919:Ihh protein, rat; D051741:Kruppel-Like Transcription Factors; C581261:MIRN125 microRNA, rat; D035683:MicroRNAs; D043562:Receptors, G-Protein-Coupled; C546888:Shh protein, rat; C498555:Smo protein, rat; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3