Increased phosphatase of regenerating liver-1 by placental stem cells promotes hepatic regeneration in a bile-duct-ligated rat model

Jong Ho Choi; Sohae Park; Gi Dae Kim; Jae Yeon Kim; Ji Hye Jun; Si Hyun Bae; Soon Koo Baik; Seong Gyu Hwang; Gi Jin Kim

doi:10.3390/cells10102530

Increased phosphatase of regenerating liver-1 by placental stem cells promotes hepatic regeneration in a bile-duct-ligated rat model

Jong Ho Choi, Sohae Park, Gi Dae Kim, Jae Yeon Kim, Ji Hye Jun, Si Hyun Bae, Soon Koo Baik, Seong Gyu Hwang, Gi Jin Kim

Internal Medicine

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Phosphatase of regenerating liver-1 (PRL-1) controls various cellular processes and liver regeneration. However, the roles of PRL-1 in liver regeneration induced by chorionic-plate-derived mesenchymal stem cells (CP-MSCs) transplantation remain unknown. Here, we found that increased PRL-1 expression by CP-MSC transplantation enhanced liver regeneration in a bile duct ligation (BDL) rat model by promoting the migration and proliferation of hepatocytes. Engrafted CP-MSCs promoted liver function via enhanced hepatocyte proliferation through increased PRL-1 expression in vivo and in vitro. Moreover, higher increased expression of PRL-1 regulated CP-MSC migration into BDL-injured rat liver through enhancement of migration-related signals by increasing Rho family proteins. The dual effects of PRL-1 on proliferation of hepatocytes and migration of CP-MSCs were substantially reduced when PRL-1 was silenced with siRNA-PRL-1 treatment. These findings suggest that PRL-1 may serve as a multifunctional enhancer for therapeutic applications of CP-MSC transplantation.

Original language	English
Article number	2530
Journal	Cells
Volume	10
Issue number	10
DOIs	https://doi.org/10.3390/cells10102530
Publication status	Published - 2021 Oct

Bibliographical note

Funding Information:
This research was supported by a grant from Ministry of Food and Drug Safety in 2021 nding: (18172MFDS182) This research and was a grant supported from by the a Korea grant from Health Ministry Technology of Food R&D and Project Drug through Safety in the 2021 Korea 172MFDS182) Health Industry and Development a grant from the Institute Korea (KHIDI), Health Technology funded by R&D the Ministry Project through of Health the & Korea Welfare, alth Republic Industry of Korea Development (grant number: Institute HI17C1050). (KHIDI), funded by the Ministry of Health & Welfare, Re-blic of Korea (grant number: HI17C1050).

Funding Information:
Figure 7. A proposed model of CP‐MSC‐induced hepatic regeneration through regulation of PRL‐1 expression. Migration of transplanted CP‐MSCs to the damaged liver tissues was regulated by a PRL‐1‐mediated Rho family signaling pathway. Engrafted CP‐MSCs stimulated hepatic regenera‐ tion in damaged liver tissues through increased PRL‐1 expression and enhanced hepatic prolifera‐ tion. in damaged liver tissues through increased PRL-1 expression and enhanced hepatic proliferation. Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Figure S1: Correlation analysis between CXCR4 and PRL‐1 expression in liver tissue of the BDL, CP‐MSC, and WI‐38 groups. Author Contributions: Conceptualization, J.H.C. and G.J.K.; methodology, J.H.C.; validation, J.Y.K.; Author Contributions: Conceptualization, J.H.C. and G.J.K.; methodology, J.H.C.; validation, J.Y.K.; formal analysis, G.D.K.; investigation, S.K.B.; data curation, S.H.B. and S.‐G.H.; writing— original draft preparation, S.P.; writing—review and editing, J.H.J.; supervision, G.J.K.; funding ac‐ quisition, G.J.K. All authors have read and agreed to the published version of the manuscript. Funding: This research was supported by a grant from Ministry of Food and Drug Safety in 2021 Funding: This research was supported by a grant from Ministry of Food and Drug Safety in 2021 (18172MFDS182) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Re‐ public of Korea (grant number: HI17C1050). Institutional Review Board Statement: All participants provided written informed consent prior to Institutional Review Board Statement: All participants provided written informed consent prior the collection of placenta. The collection and use of placentas were approved by the Institutional to the collection of placenta. The collection and use of placentas were approved by the Institutional Review Board of the Kangnam CHA General Hospital, Seoul, Korea (07–18). Additionally, the study on human liver tissuewas approved by the Institutional Review Board of Eunpyeong St. Mary’s Hospital (PC19OESI0015). The participants provided their written informed consent to participate in this study. All animal experimental processes used protocols consistent with the Institutional Review Board of CHA General Hospital, Seongnam, Korea (IACUC-130009).

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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Medicine(all)

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@article{7c726ff3f694459b96c89bc1c64856f1,

title = "Increased phosphatase of regenerating liver-1 by placental stem cells promotes hepatic regeneration in a bile-duct-ligated rat model",

abstract = "Phosphatase of regenerating liver-1 (PRL-1) controls various cellular processes and liver regeneration. However, the roles of PRL-1 in liver regeneration induced by chorionic-plate-derived mesenchymal stem cells (CP-MSCs) transplantation remain unknown. Here, we found that increased PRL-1 expression by CP-MSC transplantation enhanced liver regeneration in a bile duct ligation (BDL) rat model by promoting the migration and proliferation of hepatocytes. Engrafted CP-MSCs promoted liver function via enhanced hepatocyte proliferation through increased PRL-1 expression in vivo and in vitro. Moreover, higher increased expression of PRL-1 regulated CP-MSC migration into BDL-injured rat liver through enhancement of migration-related signals by increasing Rho family proteins. The dual effects of PRL-1 on proliferation of hepatocytes and migration of CP-MSCs were substantially reduced when PRL-1 was silenced with siRNA-PRL-1 treatment. These findings suggest that PRL-1 may serve as a multifunctional enhancer for therapeutic applications of CP-MSC transplantation.",

author = "Choi, {Jong Ho} and Sohae Park and Kim, {Gi Dae} and Kim, {Jae Yeon} and Jun, {Ji Hye} and Bae, {Si Hyun} and Baik, {Soon Koo} and Hwang, {Seong Gyu} and Kim, {Gi Jin}",

note = "Funding Information: This research was supported by a grant from Ministry of Food and Drug Safety in 2021 nding: (18172MFDS182) This research and was a grant supported from by the a Korea grant from Health Ministry Technology of Food R&D and Project Drug through Safety in the 2021 Korea 172MFDS182) Health Industry and Development a grant from the Institute Korea (KHIDI), Health Technology funded by R&D the Ministry Project through of Health the & Korea Welfare, alth Republic Industry of Korea Development (grant number: Institute HI17C1050). (KHIDI), funded by the Ministry of Health & Welfare, Re-blic of Korea (grant number: HI17C1050). Funding Information: Figure 7. A proposed model of CP‐MSC‐induced hepatic regeneration through regulation of PRL‐1 expression. Migration of transplanted CP‐MSCs to the damaged liver tissues was regulated by a PRL‐1‐mediated Rho family signaling pathway. Engrafted CP‐MSCs stimulated hepatic regenera‐ tion in damaged liver tissues through increased PRL‐1 expression and enhanced hepatic prolifera‐ tion. in damaged liver tissues through increased PRL-1 expression and enhanced hepatic proliferation. Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Figure S1: Correlation analysis between CXCR4 and PRL‐1 expression in liver tissue of the BDL, CP‐MSC, and WI‐38 groups. Author Contributions: Conceptualization, J.H.C. and G.J.K.; methodology, J.H.C.; validation, J.Y.K.; Author Contributions: Conceptualization, J.H.C. and G.J.K.; methodology, J.H.C.; validation, J.Y.K.; formal analysis, G.D.K.; investigation, S.K.B.; data curation, S.H.B. and S.‐G.H.; writing— original draft preparation, S.P.; writing—review and editing, J.H.J.; supervision, G.J.K.; funding ac‐ quisition, G.J.K. All authors have read and agreed to the published version of the manuscript. Funding: This research was supported by a grant from Ministry of Food and Drug Safety in 2021 Funding: This research was supported by a grant from Ministry of Food and Drug Safety in 2021 (18172MFDS182) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Re‐ public of Korea (grant number: HI17C1050). Institutional Review Board Statement: All participants provided written informed consent prior to Institutional Review Board Statement: All participants provided written informed consent prior the collection of placenta. The collection and use of placentas were approved by the Institutional to the collection of placenta. The collection and use of placentas were approved by the Institutional Review Board of the Kangnam CHA General Hospital, Seoul, Korea (07–18). Additionally, the study on human liver tissuewas approved by the Institutional Review Board of Eunpyeong St. Mary{\textquoteright}s Hospital (PC19OESI0015). The participants provided their written informed consent to participate in this study. All animal experimental processes used protocols consistent with the Institutional Review Board of CHA General Hospital, Seongnam, Korea (IACUC-130009). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = oct,

doi = "10.3390/cells10102530",

language = "English",

volume = "10",

journal = "Cells",

issn = "2073-4409",

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T1 - Increased phosphatase of regenerating liver-1 by placental stem cells promotes hepatic regeneration in a bile-duct-ligated rat model

AU - Choi, Jong Ho

AU - Park, Sohae

AU - Kim, Gi Dae

AU - Kim, Jae Yeon

AU - Jun, Ji Hye

AU - Bae, Si Hyun

AU - Baik, Soon Koo

AU - Hwang, Seong Gyu

AU - Kim, Gi Jin

N1 - Funding Information: This research was supported by a grant from Ministry of Food and Drug Safety in 2021 nding: (18172MFDS182) This research and was a grant supported from by the a Korea grant from Health Ministry Technology of Food R&D and Project Drug through Safety in the 2021 Korea 172MFDS182) Health Industry and Development a grant from the Institute Korea (KHIDI), Health Technology funded by R&D the Ministry Project through of Health the & Korea Welfare, alth Republic Industry of Korea Development (grant number: Institute HI17C1050). (KHIDI), funded by the Ministry of Health & Welfare, Re-blic of Korea (grant number: HI17C1050). Funding Information: Figure 7. A proposed model of CP‐MSC‐induced hepatic regeneration through regulation of PRL‐1 expression. Migration of transplanted CP‐MSCs to the damaged liver tissues was regulated by a PRL‐1‐mediated Rho family signaling pathway. Engrafted CP‐MSCs stimulated hepatic regenera‐ tion in damaged liver tissues through increased PRL‐1 expression and enhanced hepatic prolifera‐ tion. in damaged liver tissues through increased PRL-1 expression and enhanced hepatic proliferation. Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Figure S1: Correlation analysis between CXCR4 and PRL‐1 expression in liver tissue of the BDL, CP‐MSC, and WI‐38 groups. Author Contributions: Conceptualization, J.H.C. and G.J.K.; methodology, J.H.C.; validation, J.Y.K.; Author Contributions: Conceptualization, J.H.C. and G.J.K.; methodology, J.H.C.; validation, J.Y.K.; formal analysis, G.D.K.; investigation, S.K.B.; data curation, S.H.B. and S.‐G.H.; writing— original draft preparation, S.P.; writing—review and editing, J.H.J.; supervision, G.J.K.; funding ac‐ quisition, G.J.K. All authors have read and agreed to the published version of the manuscript. Funding: This research was supported by a grant from Ministry of Food and Drug Safety in 2021 Funding: This research was supported by a grant from Ministry of Food and Drug Safety in 2021 (18172MFDS182) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Re‐ public of Korea (grant number: HI17C1050). Institutional Review Board Statement: All participants provided written informed consent prior to Institutional Review Board Statement: All participants provided written informed consent prior the collection of placenta. The collection and use of placentas were approved by the Institutional to the collection of placenta. The collection and use of placentas were approved by the Institutional Review Board of the Kangnam CHA General Hospital, Seoul, Korea (07–18). Additionally, the study on human liver tissuewas approved by the Institutional Review Board of Eunpyeong St. Mary’s Hospital (PC19OESI0015). The participants provided their written informed consent to participate in this study. All animal experimental processes used protocols consistent with the Institutional Review Board of CHA General Hospital, Seongnam, Korea (IACUC-130009). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/10

Y1 - 2021/10

N2 - Phosphatase of regenerating liver-1 (PRL-1) controls various cellular processes and liver regeneration. However, the roles of PRL-1 in liver regeneration induced by chorionic-plate-derived mesenchymal stem cells (CP-MSCs) transplantation remain unknown. Here, we found that increased PRL-1 expression by CP-MSC transplantation enhanced liver regeneration in a bile duct ligation (BDL) rat model by promoting the migration and proliferation of hepatocytes. Engrafted CP-MSCs promoted liver function via enhanced hepatocyte proliferation through increased PRL-1 expression in vivo and in vitro. Moreover, higher increased expression of PRL-1 regulated CP-MSC migration into BDL-injured rat liver through enhancement of migration-related signals by increasing Rho family proteins. The dual effects of PRL-1 on proliferation of hepatocytes and migration of CP-MSCs were substantially reduced when PRL-1 was silenced with siRNA-PRL-1 treatment. These findings suggest that PRL-1 may serve as a multifunctional enhancer for therapeutic applications of CP-MSC transplantation.

AB - Phosphatase of regenerating liver-1 (PRL-1) controls various cellular processes and liver regeneration. However, the roles of PRL-1 in liver regeneration induced by chorionic-plate-derived mesenchymal stem cells (CP-MSCs) transplantation remain unknown. Here, we found that increased PRL-1 expression by CP-MSC transplantation enhanced liver regeneration in a bile duct ligation (BDL) rat model by promoting the migration and proliferation of hepatocytes. Engrafted CP-MSCs promoted liver function via enhanced hepatocyte proliferation through increased PRL-1 expression in vivo and in vitro. Moreover, higher increased expression of PRL-1 regulated CP-MSC migration into BDL-injured rat liver through enhancement of migration-related signals by increasing Rho family proteins. The dual effects of PRL-1 on proliferation of hepatocytes and migration of CP-MSCs were substantially reduced when PRL-1 was silenced with siRNA-PRL-1 treatment. These findings suggest that PRL-1 may serve as a multifunctional enhancer for therapeutic applications of CP-MSC transplantation.

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U2 - 10.3390/cells10102530

DO - 10.3390/cells10102530

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Increased phosphatase of regenerating liver-1 by placental stem cells promotes hepatic regeneration in a bile-duct-ligated rat model

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