α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells.
Endothelial cells (ECs) express fibroblast growth factor (FGF) receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5413063?pdf=render |
| _version_ | 1819118424592220160 |
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| author | Chih-Ping Chung Yu-Chun Chang Yan Ding Kenneth Lim Qinghua Liu Langjing Zhu Wei Zhang Tzong-Shi Lu Guerman Molostvov Daniel Zehnder Li-Li Hsiao |
| author_facet | Chih-Ping Chung Yu-Chun Chang Yan Ding Kenneth Lim Qinghua Liu Langjing Zhu Wei Zhang Tzong-Shi Lu Guerman Molostvov Daniel Zehnder Li-Li Hsiao |
| author_sort | Chih-Ping Chung |
| collection | DOAJ |
| description | Endothelial cells (ECs) express fibroblast growth factor (FGF) receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klotho expression within the human vascular tree and to investigate the potential role of α-Klotho in determining FGF-23 mediated EC regulation. Human tissue and ECs from various organs were used for immunohistochemistry and Western blot. Primary cultures of human aortic endothelial cells (HAECs) and human brain microvascular endothelial cells (HBMECs) were used to generate in vitro cell models. We found endogenous α-Klotho expression in ECs from various organs except in microvascular ECs from human brain. Furthermore, FGF-23 stimulated endothelial nitric oxide synthase (eNOS) expression, nitric oxide (NO) production, and cell proliferation in HAECs. Interestingly, these effects were not observed in our HBMEC model in vitro. High phosphate treatment and endothelial α-Klotho knockdown mitigated FGF-23 mediated eNOS induction, NO production, and cell proliferation in HAECs. Rescue treatment with soluble α-Klotho did not reverse endothelial FGF-23 resistance caused by reduced or absent α-Klotho expression in HAECs. These novel observations provide evidence for differential α-Klotho functional expression in the human endothelium and its presence may play a role in determining the response to FGF-23 in the vascular tree. α-Klotho was not detected in cerebral microvascular ECs and its absence may render these cells nonresponsive to FGF-23. |
| first_indexed | 2024-12-22T05:48:40Z |
| format | Article |
| id | doaj.art-346bb04213c94d848fc1d1a436b58338 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T05:48:40Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-346bb04213c94d848fc1d1a436b583382022-12-21T18:36:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017681710.1371/journal.pone.0176817α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells.Chih-Ping ChungYu-Chun ChangYan DingKenneth LimQinghua LiuLangjing ZhuWei ZhangTzong-Shi LuGuerman MolostvovDaniel ZehnderLi-Li HsiaoEndothelial cells (ECs) express fibroblast growth factor (FGF) receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klotho expression within the human vascular tree and to investigate the potential role of α-Klotho in determining FGF-23 mediated EC regulation. Human tissue and ECs from various organs were used for immunohistochemistry and Western blot. Primary cultures of human aortic endothelial cells (HAECs) and human brain microvascular endothelial cells (HBMECs) were used to generate in vitro cell models. We found endogenous α-Klotho expression in ECs from various organs except in microvascular ECs from human brain. Furthermore, FGF-23 stimulated endothelial nitric oxide synthase (eNOS) expression, nitric oxide (NO) production, and cell proliferation in HAECs. Interestingly, these effects were not observed in our HBMEC model in vitro. High phosphate treatment and endothelial α-Klotho knockdown mitigated FGF-23 mediated eNOS induction, NO production, and cell proliferation in HAECs. Rescue treatment with soluble α-Klotho did not reverse endothelial FGF-23 resistance caused by reduced or absent α-Klotho expression in HAECs. These novel observations provide evidence for differential α-Klotho functional expression in the human endothelium and its presence may play a role in determining the response to FGF-23 in the vascular tree. α-Klotho was not detected in cerebral microvascular ECs and its absence may render these cells nonresponsive to FGF-23.http://europepmc.org/articles/PMC5413063?pdf=render |
| spellingShingle | Chih-Ping Chung Yu-Chun Chang Yan Ding Kenneth Lim Qinghua Liu Langjing Zhu Wei Zhang Tzong-Shi Lu Guerman Molostvov Daniel Zehnder Li-Li Hsiao α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells. PLoS ONE |
| title | α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells. |
| title_full | α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells. |
| title_fullStr | α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells. |
| title_full_unstemmed | α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells. |
| title_short | α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells. |
| title_sort | α klotho expression determines nitric oxide synthesis in response to fgf 23 in human aortic endothelial cells |
| url | http://europepmc.org/articles/PMC5413063?pdf=render |
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