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Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway

BACKGROUND: Vascular abnormalities in the ovary cause infertility accompanied by ovarian insufficiency due to a microenvironment of barren ovarian tissues. Placenta-derived mesenchymal stem cells (PD-MSCs, Naïve) treatment in ovarian dysfunction shows angiogenic effect, however, the therapeutic mech...

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Autores principales: Park, Hyeri, Seok, Jin, You, Jun Hyeong, Kim, Jae Yeon, Lim, Ja-Yun, Kim, Gi Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900363/
https://www.ncbi.nlm.nih.gov/pubmed/35255961
http://dx.doi.org/10.1186/s13287-022-02772-9
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author Park, Hyeri
Seok, Jin
You, Jun Hyeong
Kim, Jae Yeon
Lim, Ja-Yun
Kim, Gi Jin
author_facet Park, Hyeri
Seok, Jin
You, Jun Hyeong
Kim, Jae Yeon
Lim, Ja-Yun
Kim, Gi Jin
author_sort Park, Hyeri
collection PubMed
description BACKGROUND: Vascular abnormalities in the ovary cause infertility accompanied by ovarian insufficiency due to a microenvironment of barren ovarian tissues. Placenta-derived mesenchymal stem cells (PD-MSCs, Naïve) treatment in ovarian dysfunction shows angiogenic effect, however, the therapeutic mechanism between ovarian function and vascular remodeling still unclear. Therefore, we examined whether by phosphatase regenerating liver-1 (PRL-1), which is correlated with angiogenesis in reproductive systems, overexpressed PD-MSCs could maximize the angiogenic effects in an ovarian tissues injured of rat model with partial ovariectomy and their therapeutic mechanism by enhanced vascular function via PDGF signaling. METHODS: PD-MSCs(PRL-1) (PRL-1) were generated by nonviral AMAXA gene delivery system and analyzed the vascular remodeling and follicular development in ovary. One week after Sprague–Dawley (SD) rats ovariectomy, Naïve and PRL-1 was transplanted. The animals were sacrificed at 1, 3 and 5 weeks after transplantation and vascular remodeling and follicular development were analyzed. Also, human umbilical vein endothelial cells (HUVECs) and ovarian explantation culture were performed to prove the specific effects and mechanism of PRL-1. RESULTS: Vascular structures in ovarian tissues (e.g., number of vessels, thickness and lumen area) showed changes in the Naïve and PRL-1-overexpressed PD-MSC (PRL-1) transplantation (Tx) groups compared to the nontransplantation (NTx) group. Especially, PRL-1 induce to increase the expression of platelet-derived growth factor (PDGF), which plays a role in vascular remodeling as well as follicular development, compared to the NTx. Also, the expression of genes related to pericyte and vascular permeability in arteries was significantly enhanced in the PRL-1 compared to the NTx (p < 0.05). PRL-1 enhanced the vascular formation and permeability of human umbilical vein endothelial cells (HUVECs) via activated the PDGF signaling pathway. CONCLUSIONS: Our results show that PRL-1 restored ovarian function by enhanced vascular function via PDGF signaling pathway. These findings offer new insight into the effects of functionally enhanced stem cell therapy for reproductive systems and should provide new avenues to develop more efficient therapies in degenerative medicine. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02772-9.
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spelling pubmed-89003632022-03-17 Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway Park, Hyeri Seok, Jin You, Jun Hyeong Kim, Jae Yeon Lim, Ja-Yun Kim, Gi Jin Stem Cell Res Ther Research BACKGROUND: Vascular abnormalities in the ovary cause infertility accompanied by ovarian insufficiency due to a microenvironment of barren ovarian tissues. Placenta-derived mesenchymal stem cells (PD-MSCs, Naïve) treatment in ovarian dysfunction shows angiogenic effect, however, the therapeutic mechanism between ovarian function and vascular remodeling still unclear. Therefore, we examined whether by phosphatase regenerating liver-1 (PRL-1), which is correlated with angiogenesis in reproductive systems, overexpressed PD-MSCs could maximize the angiogenic effects in an ovarian tissues injured of rat model with partial ovariectomy and their therapeutic mechanism by enhanced vascular function via PDGF signaling. METHODS: PD-MSCs(PRL-1) (PRL-1) were generated by nonviral AMAXA gene delivery system and analyzed the vascular remodeling and follicular development in ovary. One week after Sprague–Dawley (SD) rats ovariectomy, Naïve and PRL-1 was transplanted. The animals were sacrificed at 1, 3 and 5 weeks after transplantation and vascular remodeling and follicular development were analyzed. Also, human umbilical vein endothelial cells (HUVECs) and ovarian explantation culture were performed to prove the specific effects and mechanism of PRL-1. RESULTS: Vascular structures in ovarian tissues (e.g., number of vessels, thickness and lumen area) showed changes in the Naïve and PRL-1-overexpressed PD-MSC (PRL-1) transplantation (Tx) groups compared to the nontransplantation (NTx) group. Especially, PRL-1 induce to increase the expression of platelet-derived growth factor (PDGF), which plays a role in vascular remodeling as well as follicular development, compared to the NTx. Also, the expression of genes related to pericyte and vascular permeability in arteries was significantly enhanced in the PRL-1 compared to the NTx (p < 0.05). PRL-1 enhanced the vascular formation and permeability of human umbilical vein endothelial cells (HUVECs) via activated the PDGF signaling pathway. CONCLUSIONS: Our results show that PRL-1 restored ovarian function by enhanced vascular function via PDGF signaling pathway. These findings offer new insight into the effects of functionally enhanced stem cell therapy for reproductive systems and should provide new avenues to develop more efficient therapies in degenerative medicine. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02772-9. BioMed Central 2022-03-07 /pmc/articles/PMC8900363/ /pubmed/35255961 http://dx.doi.org/10.1186/s13287-022-02772-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Park, Hyeri
Seok, Jin
You, Jun Hyeong
Kim, Jae Yeon
Lim, Ja-Yun
Kim, Gi Jin
Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway
title Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway
title_full Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway
title_fullStr Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway
title_full_unstemmed Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway
title_short Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway
title_sort increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900363/
https://www.ncbi.nlm.nih.gov/pubmed/35255961
http://dx.doi.org/10.1186/s13287-022-02772-9
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