Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro
Somatostatin is an inhibitory peptide, which regulates the release of several hormones, and affects neurotransmission and cell proliferation via its five G<sub>i</sub> protein-coupled receptors (SST<sub>1-5</sub>). Although its endocrine regulatory and anti-tumour effects hav...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/3098 |
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| author | Muhammad Aslam Hafiza Idrees Peter Ferdinandy Zsuzsanna Helyes Christian Hamm Rainer Schulz |
| author_facet | Muhammad Aslam Hafiza Idrees Peter Ferdinandy Zsuzsanna Helyes Christian Hamm Rainer Schulz |
| author_sort | Muhammad Aslam |
| collection | DOAJ |
| description | Somatostatin is an inhibitory peptide, which regulates the release of several hormones, and affects neurotransmission and cell proliferation via its five G<sub>i</sub> protein-coupled receptors (SST<sub>1-5</sub>). Although its endocrine regulatory and anti-tumour effects have been thoroughly studied, little is known about its effect on the vascular system. The aim of the present study was to analyse the effects and potential mechanisms of somatostatin on endothelial barrier function. Cultured human umbilical vein endothelial cells (HUVECs) express mainly SST<sub>1</sub> and SST<sub>5</sub> receptors. Somatostatin did not affect the basal HUVEC permeability, but primed HUVEC monolayers for thrombin-induced hyperpermeability. Western blot data demonstrated that somatostatin activated the phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (MAPK) pathways by phosphorylation. The HUVEC barrier destabilizing effects were abrogated by pre-treating HUVECs with mitogen-activated protein kinase kinase/extracellular signal regulated kinase (MEK/ERK), but not the Akt inhibitor. Moreover, somatostatin pre-treatment amplified vascular endothelial growth factor (VEGF)-induced angiogenesis (3D spheroid formation) in HUVECs. In conclusion, the data demonstrate that HUVECs under quiescence conditions express SST<sub>1</sub> and SST<sub>5</sub> receptors. Moreover, somatostatin primes HUVECs for thrombin-induced hyperpermeability mainly via the activation of MEK/ERK signalling and promotes HUVEC proliferation and angiogenesis in vitro. |
| first_indexed | 2024-03-09T19:42:56Z |
| format | Article |
| id | doaj.art-f7c6fa01106049cda886d317a3cece94 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:42:56Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f7c6fa01106049cda886d317a3cece942023-11-24T01:32:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236309810.3390/ijms23063098Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In VitroMuhammad Aslam0Hafiza Idrees1Peter Ferdinandy2Zsuzsanna Helyes3Christian Hamm4Rainer Schulz5Experimental Cardiology, Department of Cardiology and Angiology, Justus Liebig University, Aulweg 129, 35392 Giessen, GermanyExperimental Cardiology, Department of Cardiology and Angiology, Justus Liebig University, Aulweg 129, 35392 Giessen, GermanyDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School and Szentágothai Research Centre, University of Pécs, 7624 Pécs, HungaryExperimental Cardiology, Department of Cardiology and Angiology, Justus Liebig University, Aulweg 129, 35392 Giessen, GermanyInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanySomatostatin is an inhibitory peptide, which regulates the release of several hormones, and affects neurotransmission and cell proliferation via its five G<sub>i</sub> protein-coupled receptors (SST<sub>1-5</sub>). Although its endocrine regulatory and anti-tumour effects have been thoroughly studied, little is known about its effect on the vascular system. The aim of the present study was to analyse the effects and potential mechanisms of somatostatin on endothelial barrier function. Cultured human umbilical vein endothelial cells (HUVECs) express mainly SST<sub>1</sub> and SST<sub>5</sub> receptors. Somatostatin did not affect the basal HUVEC permeability, but primed HUVEC monolayers for thrombin-induced hyperpermeability. Western blot data demonstrated that somatostatin activated the phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (MAPK) pathways by phosphorylation. The HUVEC barrier destabilizing effects were abrogated by pre-treating HUVECs with mitogen-activated protein kinase kinase/extracellular signal regulated kinase (MEK/ERK), but not the Akt inhibitor. Moreover, somatostatin pre-treatment amplified vascular endothelial growth factor (VEGF)-induced angiogenesis (3D spheroid formation) in HUVECs. In conclusion, the data demonstrate that HUVECs under quiescence conditions express SST<sub>1</sub> and SST<sub>5</sub> receptors. Moreover, somatostatin primes HUVECs for thrombin-induced hyperpermeability mainly via the activation of MEK/ERK signalling and promotes HUVEC proliferation and angiogenesis in vitro.https://www.mdpi.com/1422-0067/23/6/3098somatostatin receptorsAktMAPKangiogenesisendothelial permeabilityRhoA/Rock |
| spellingShingle | Muhammad Aslam Hafiza Idrees Peter Ferdinandy Zsuzsanna Helyes Christian Hamm Rainer Schulz Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro International Journal of Molecular Sciences somatostatin receptors Akt MAPK angiogenesis endothelial permeability RhoA/Rock |
| title | Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro |
| title_full | Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro |
| title_fullStr | Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro |
| title_full_unstemmed | Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro |
| title_short | Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro |
| title_sort | somatostatin primes endothelial cells for agonist induced hyperpermeability and angiogenesis in vitro |
| topic | somatostatin receptors Akt MAPK angiogenesis endothelial permeability RhoA/Rock |
| url | https://www.mdpi.com/1422-0067/23/6/3098 |
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