Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway
Abstract 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 therapeu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-02772-9 |
| _version_ | 1818245593352372224 |
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| author | Hyeri Park Jin Seok Jun Hyeong You Jae Yeon Kim Ja-Yun Lim Gi Jin Kim |
| author_facet | Hyeri Park Jin Seok Jun Hyeong You Jae Yeon Kim Ja-Yun Lim Gi Jin Kim |
| author_sort | Hyeri Park |
| collection | DOAJ |
| description | Abstract 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-MSCsPRL-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. |
| first_indexed | 2024-12-12T14:35:23Z |
| format | Article |
| id | doaj.art-71a8de29de7843c1860a9e8fc832c4ec |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-12T14:35:23Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-71a8de29de7843c1860a9e8fc832c4ec2022-12-22T00:21:23ZengBMCStem Cell Research & Therapy1757-65122022-03-0113111610.1186/s13287-022-02772-9Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathwayHyeri Park0Jin Seok1Jun Hyeong You2Jae Yeon Kim3Ja-Yun Lim4Gi Jin Kim5Department of Biomedical Science, CHA UniversityDepartment of Biomedical Science, CHA UniversityDepartment of Biomedical Science, CHA UniversityDepartment of Biomedical Science, CHA UniversityDepartment of Health and Environmental Science, Korea UniversityDepartment of Biomedical Science, CHA UniversityAbstract 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-MSCsPRL-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.https://doi.org/10.1186/s13287-022-02772-9Placenta-derived mesenchymal stem cellsPhosphatase regenerating liver-1OvaryFolliculogenesisVascular remodelingPlatelet-derived growth factor |
| spellingShingle | Hyeri Park Jin Seok Jun Hyeong You Jae Yeon Kim Ja-Yun Lim Gi Jin Kim Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway Stem Cell Research & Therapy Placenta-derived mesenchymal stem cells Phosphatase regenerating liver-1 Ovary Folliculogenesis Vascular remodeling Platelet-derived growth factor |
| 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 | Placenta-derived mesenchymal stem cells Phosphatase regenerating liver-1 Ovary Folliculogenesis Vascular remodeling Platelet-derived growth factor |
| url | https://doi.org/10.1186/s13287-022-02772-9 |
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