Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells
Myriam Iglewski, Stephen R GrantDepartment of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, USAAbstract: The urotensin II receptor, bound by the ligand urotensin II, generates second ­messengers, ie, inositol triphosphate and diacylglycerol,...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2010-08-01
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| Series: | Vascular Health and Risk Management |
| Online Access: | http://www.dovepress.com/urotensin-ii-induced-signaling-involved-in-proliferation-of-vascular-s-a5025 |
| _version_ | 1811319071298289664 |
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| author | Myriam Iglewski Stephen R Grant |
| author_facet | Myriam Iglewski Stephen R Grant |
| author_sort | Myriam Iglewski |
| collection | DOAJ |
| description | Myriam Iglewski, Stephen R GrantDepartment of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, USAAbstract: The urotensin II receptor, bound by the ligand urotensin II, generates second ­messengers, ie, inositol triphosphate and diacylglycerol, which stimulate the subsequent release of calcium (Ca2+) in vascular smooth muscle cells. Ca2+ influx leads to the activation of Ca2+-dependent kinases (CaMK) via calmodulin binding, resulting in cellular proliferation. We hypothesize that urotensin II signaling in pulmonary arterial vascular smooth muscle cells (Pac1) and primary aortic vascular smooth muscle cells (PAVSMC) results in phosphorylation of Ca2+/calmodulin-dependent kinases leading to cellular proliferation. Exposure of Pac1 cultures to urotensin II increased intracellular Ca2+, subsequently activating Ca2+/calmodulin-dependent kinase kinase (CaMKK), and Ca2+/calmodulin-dependent kinase Type I (CaMKI), extracellular signal-regulated kinase (ERK 1/2), and protein kinase D. Treatment of Pac1 and PAVSMC with urotensin II increased proliferation as measured by 3H-thymidine uptake. The urotensin II-induced increase in 3H-thymidine incorporation was inhibited by a CaMKK inhibitor. Taken together, our results demonstrate that urotensin II stimulation of smooth muscle cells leads to a Ca2+/calmodulin-dependent kinase-mediated increase in cellular proliferation.Keywords: urotensin II receptor, CaMKI, hypertrophy, CaMKK, protein kinase D |
| first_indexed | 2024-04-13T12:35:52Z |
| format | Article |
| id | doaj.art-e9d1fdebcaff418891c0b8cede7f4050 |
| institution | Directory Open Access Journal |
| issn | 1176-6344 1178-2048 |
| language | English |
| last_indexed | 2024-04-13T12:35:52Z |
| publishDate | 2010-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Vascular Health and Risk Management |
| spelling | doaj.art-e9d1fdebcaff418891c0b8cede7f40502022-12-22T02:46:40ZengDove Medical PressVascular Health and Risk Management1176-63441178-20482010-08-012010default723734Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cellsMyriam IglewskiStephen R GrantMyriam Iglewski, Stephen R GrantDepartment of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, USAAbstract: The urotensin II receptor, bound by the ligand urotensin II, generates second ­messengers, ie, inositol triphosphate and diacylglycerol, which stimulate the subsequent release of calcium (Ca2+) in vascular smooth muscle cells. Ca2+ influx leads to the activation of Ca2+-dependent kinases (CaMK) via calmodulin binding, resulting in cellular proliferation. We hypothesize that urotensin II signaling in pulmonary arterial vascular smooth muscle cells (Pac1) and primary aortic vascular smooth muscle cells (PAVSMC) results in phosphorylation of Ca2+/calmodulin-dependent kinases leading to cellular proliferation. Exposure of Pac1 cultures to urotensin II increased intracellular Ca2+, subsequently activating Ca2+/calmodulin-dependent kinase kinase (CaMKK), and Ca2+/calmodulin-dependent kinase Type I (CaMKI), extracellular signal-regulated kinase (ERK 1/2), and protein kinase D. Treatment of Pac1 and PAVSMC with urotensin II increased proliferation as measured by 3H-thymidine uptake. The urotensin II-induced increase in 3H-thymidine incorporation was inhibited by a CaMKK inhibitor. Taken together, our results demonstrate that urotensin II stimulation of smooth muscle cells leads to a Ca2+/calmodulin-dependent kinase-mediated increase in cellular proliferation.Keywords: urotensin II receptor, CaMKI, hypertrophy, CaMKK, protein kinase Dhttp://www.dovepress.com/urotensin-ii-induced-signaling-involved-in-proliferation-of-vascular-s-a5025 |
| spellingShingle | Myriam Iglewski Stephen R Grant Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells Vascular Health and Risk Management |
| title | Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells |
| title_full | Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells |
| title_fullStr | Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells |
| title_full_unstemmed | Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells |
| title_short | Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells |
| title_sort | urotensin ii induced signaling involved in proliferation of vascular smooth muscle cells |
| url | http://www.dovepress.com/urotensin-ii-induced-signaling-involved-in-proliferation-of-vascular-s-a5025 |
| work_keys_str_mv | AT myriamiglewski urotensiniiinducedsignalinginvolvedinproliferationofvascularsmoothmusclecells AT stephenrgrant urotensiniiinducedsignalinginvolvedinproliferationofvascularsmoothmusclecells |