Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling
Background/Aim: Reduction in serum placental growth factor (PLGF) frequently co-occurs with preeclampsia (PE) and gestational diabetes mellitus (GDM). Recently, we reported that impairment in gestational beta-cell mass growth may result from PE-associated reduction in PLGF and lead to development of...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2015-04-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/374051 |
| _version_ | 1811194177050902528 |
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| author | Jun Li Huanchun Ying Guiyang Cai Quan Guo Lizhu Chen |
| author_facet | Jun Li Huanchun Ying Guiyang Cai Quan Guo Lizhu Chen |
| author_sort | Jun Li |
| collection | DOAJ |
| description | Background/Aim: Reduction in serum placental growth factor (PLGF) frequently co-occurs with preeclampsia (PE) and gestational diabetes mellitus (GDM). Recently, we reported that impairment in gestational beta-cell mass growth may result from PE-associated reduction in PLGF and lead to development of GDM. Here, we studied the underlying mechanisms. Methods: We co-cultured primary mouse beta cells with mouse islet endothelial cells (MS1), with or without PLGF. We also cultured beta cells in conditioned media from PLGF-treated MS1. Specific signal-pathway inhibitors were applied to cultured beta cells in conditioned media from PLGF-treated MS1. We analysed beta-cell proliferation by BrdU incorporation. We analysed changes in cell number by a MTT assay. We analysed protein levels of cell-cycle regulators in beta cells by Western blot. Results: PLGF itself failed to induce beta-cell proliferation, but significantly augmented proliferation of beta cells co-cultured with MS1, which resulted in significant increases in cell number. Conditioned media from the PLGF-treated MS1 cells similarly induced beta-cell proliferation, which was abolished by inhibition of PI3k/Akt signalling, but not by inhibition of either ERK/MAPK or JNK signalling. The induction of beta-cell proliferation by PLGF-treated MS1 cells appeared to involve decreases in cell-cycle inhibitors p21 and p27, and increases in cell-cycle activators CDK4 and CyclinD1. Conclusion: Gestational PLGF may target islet endothelial cells to release growth factors that activate PI3k/Akt signalling in beta cells to increase their proliferation. PE-associated reduction in PLGF impairs these processes to result in GDM. |
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| format | Article |
| id | doaj.art-c7fc78eca11d479ab33e92b42c76bf73 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-12T00:22:38Z |
| publishDate | 2015-04-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-c7fc78eca11d479ab33e92b42c76bf732022-12-22T03:55:41ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-04-01361344310.1159/000374051374051Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k SignallingJun LiHuanchun YingGuiyang CaiQuan GuoLizhu ChenBackground/Aim: Reduction in serum placental growth factor (PLGF) frequently co-occurs with preeclampsia (PE) and gestational diabetes mellitus (GDM). Recently, we reported that impairment in gestational beta-cell mass growth may result from PE-associated reduction in PLGF and lead to development of GDM. Here, we studied the underlying mechanisms. Methods: We co-cultured primary mouse beta cells with mouse islet endothelial cells (MS1), with or without PLGF. We also cultured beta cells in conditioned media from PLGF-treated MS1. Specific signal-pathway inhibitors were applied to cultured beta cells in conditioned media from PLGF-treated MS1. We analysed beta-cell proliferation by BrdU incorporation. We analysed changes in cell number by a MTT assay. We analysed protein levels of cell-cycle regulators in beta cells by Western blot. Results: PLGF itself failed to induce beta-cell proliferation, but significantly augmented proliferation of beta cells co-cultured with MS1, which resulted in significant increases in cell number. Conditioned media from the PLGF-treated MS1 cells similarly induced beta-cell proliferation, which was abolished by inhibition of PI3k/Akt signalling, but not by inhibition of either ERK/MAPK or JNK signalling. The induction of beta-cell proliferation by PLGF-treated MS1 cells appeared to involve decreases in cell-cycle inhibitors p21 and p27, and increases in cell-cycle activators CDK4 and CyclinD1. Conclusion: Gestational PLGF may target islet endothelial cells to release growth factors that activate PI3k/Akt signalling in beta cells to increase their proliferation. PE-associated reduction in PLGF impairs these processes to result in GDM.http://www.karger.com/Article/FullText/374051PreeclampsiaPlacental growth factorBeta cell proliferationMS1, PI3k signalingGestational diabetes mellitus |
| spellingShingle | Jun Li Huanchun Ying Guiyang Cai Quan Guo Lizhu Chen Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling Cellular Physiology and Biochemistry Preeclampsia Placental growth factor Beta cell proliferation MS1, PI3k signaling Gestational diabetes mellitus |
| title | Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling |
| title_full | Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling |
| title_fullStr | Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling |
| title_full_unstemmed | Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling |
| title_short | Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling |
| title_sort | pre eclampsia associated reduction in placental growth factor impaired beta cell proliferation through pi3k signalling |
| topic | Preeclampsia Placental growth factor Beta cell proliferation MS1, PI3k signaling Gestational diabetes mellitus |
| url | http://www.karger.com/Article/FullText/374051 |
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