Dynamic regulation of miRNA expression by functionally enhanced placental mesenchymal stem cells promoteshepatic regeneration in a rat model with bile duct ligation

Jae Yeon Kim, Ji Hye Jun, Soo Young Park, Seong Wook Yang, Si Hyun Bae, Gi Jin Kim

Research output: Contribution to journalArticle

Abstract

Placenta-derived mesenchymal stem cells (PD-MSCs) were highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs (miRNAs)were found to mediate one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with migrated naïve PD-MSCs, migrated PRL-1(+) PD-MSCs showed improved integrin-dependent migration abilitythrough Ras homolog (RHO) family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplantedPRL-1(+) PD-MSCs through the integrin family. Additionally, an increase inplatelet-derived growth factor receptor A (PDGFRA) by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSC transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs byactivating the interleukin-6 (IL-6) signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understandingof therapeutic mechanisms based on miRNA-mediated stem-cell therapy in liver diseases.

Original languageEnglish
Article number5299
JournalInternational journal of molecular sciences
Volume20
Issue number21
DOIs
Publication statusPublished - 2019 Nov 1

Fingerprint

stem cells
Bile Ducts
Stem cells
MicroRNAs
Mesenchymal Stromal Cells
regeneration
ducts
Ducts
Placenta
rats
Ligation
Rats
Regeneration
liver
Liver
Integrins
Mesenchymal Stem Cell Transplantation
Tissue
interleukins
Regenerative Medicine

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

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title = "Dynamic regulation of miRNA expression by functionally enhanced placental mesenchymal stem cells promoteshepatic regeneration in a rat model with bile duct ligation",
abstract = "Placenta-derived mesenchymal stem cells (PD-MSCs) were highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs (miRNAs)were found to mediate one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with migrated na{\"i}ve PD-MSCs, migrated PRL-1(+) PD-MSCs showed improved integrin-dependent migration abilitythrough Ras homolog (RHO) family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplantedPRL-1(+) PD-MSCs through the integrin family. Additionally, an increase inplatelet-derived growth factor receptor A (PDGFRA) by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSC transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs byactivating the interleukin-6 (IL-6) signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understandingof therapeutic mechanisms based on miRNA-mediated stem-cell therapy in liver diseases.",
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Dynamic regulation of miRNA expression by functionally enhanced placental mesenchymal stem cells promoteshepatic regeneration in a rat model with bile duct ligation. / Kim, Jae Yeon; Jun, Ji Hye; Park, Soo Young; Yang, Seong Wook; Bae, Si Hyun; Kim, Gi Jin.

In: International journal of molecular sciences, Vol. 20, No. 21, 5299, 01.11.2019.

Research output: Contribution to journalArticle

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T1 - Dynamic regulation of miRNA expression by functionally enhanced placental mesenchymal stem cells promoteshepatic regeneration in a rat model with bile duct ligation

AU - Kim, Jae Yeon

AU - Jun, Ji Hye

AU - Park, Soo Young

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