CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier
Cerebral cavernous malformations (CCMs) arise when capillaries within the brain enlarge abnormally, causing the blood–brain barrier (BBB) to break down. The BBB serves as a sophisticated interface that controls molecular interactions between the bloodstream and the central nervous system. The neurov...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/13/5/751 |
| _version_ | 1797599554131984384 |
|---|---|
| author | Revathi Gnanasekaran Justin Aickareth Majd Hawwar Nickolas Sanchez Jacob Croft Jun Zhang |
| author_facet | Revathi Gnanasekaran Justin Aickareth Majd Hawwar Nickolas Sanchez Jacob Croft Jun Zhang |
| author_sort | Revathi Gnanasekaran |
| collection | DOAJ |
| description | Cerebral cavernous malformations (CCMs) arise when capillaries within the brain enlarge abnormally, causing the blood–brain barrier (BBB) to break down. The BBB serves as a sophisticated interface that controls molecular interactions between the bloodstream and the central nervous system. The neurovascular unit (NVU) is a complex structure made up of neurons, astrocytes, endothelial cells (ECs), pericytes, microglia, and basement membranes, which work together to maintain blood–brain barrier (BBB) permeability. Within the NVU, tight junctions (TJs) and adherens junctions (AJs) between endothelial cells play a critical role in regulating the permeability of the BBB. Disruptions to these junctions can compromise the BBB, potentially leading to a hemorrhagic stroke. Understanding the molecular signaling cascades that regulate BBB permeability through EC junctions is, therefore, essential. New research has demonstrated that steroids, including estrogens (ESTs), glucocorticoids (GCs), and metabolites/derivatives of progesterone (PRGs), have multifaceted effects on blood–brain barrier (BBB) permeability by regulating the expression of tight junctions (TJs) and adherens junctions (AJs). They also have anti-inflammatory effects on blood vessels. PRGs, in particular, have been found to play a significant role in maintaining BBB integrity. PRGs act through a combination of its classic and non-classic PRG receptors (nPR/mPR), which are part of a signaling network known as the CCM signaling complex (CSC). This network couples both nPR and mPR in the CmPn/CmP pathway in endothelial cells (ECs). |
| first_indexed | 2024-03-11T03:35:58Z |
| format | Article |
| id | doaj.art-da11fd3380914a37b4c8bf8e3e9a6287 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T03:35:58Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-da11fd3380914a37b4c8bf8e3e9a62872023-11-18T02:03:36ZengMDPI AGJournal of Personalized Medicine2075-44262023-04-0113575110.3390/jpm13050751CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel BarrierRevathi Gnanasekaran0Justin Aickareth1Majd Hawwar2Nickolas Sanchez3Jacob Croft4Jun Zhang5Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, El Paso, TX 79905, USADepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, El Paso, TX 79905, USADepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, El Paso, TX 79905, USADepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, El Paso, TX 79905, USADepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, El Paso, TX 79905, USADepartment of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, El Paso, TX 79905, USACerebral cavernous malformations (CCMs) arise when capillaries within the brain enlarge abnormally, causing the blood–brain barrier (BBB) to break down. The BBB serves as a sophisticated interface that controls molecular interactions between the bloodstream and the central nervous system. The neurovascular unit (NVU) is a complex structure made up of neurons, astrocytes, endothelial cells (ECs), pericytes, microglia, and basement membranes, which work together to maintain blood–brain barrier (BBB) permeability. Within the NVU, tight junctions (TJs) and adherens junctions (AJs) between endothelial cells play a critical role in regulating the permeability of the BBB. Disruptions to these junctions can compromise the BBB, potentially leading to a hemorrhagic stroke. Understanding the molecular signaling cascades that regulate BBB permeability through EC junctions is, therefore, essential. New research has demonstrated that steroids, including estrogens (ESTs), glucocorticoids (GCs), and metabolites/derivatives of progesterone (PRGs), have multifaceted effects on blood–brain barrier (BBB) permeability by regulating the expression of tight junctions (TJs) and adherens junctions (AJs). They also have anti-inflammatory effects on blood vessels. PRGs, in particular, have been found to play a significant role in maintaining BBB integrity. PRGs act through a combination of its classic and non-classic PRG receptors (nPR/mPR), which are part of a signaling network known as the CCM signaling complex (CSC). This network couples both nPR and mPR in the CmPn/CmP pathway in endothelial cells (ECs).https://www.mdpi.com/2075-4426/13/5/751cerebral cavernous malformationsCCM signaling complexblood-brain barriertight junctions and adherens junctionendothelial cellsprogesterone |
| spellingShingle | Revathi Gnanasekaran Justin Aickareth Majd Hawwar Nickolas Sanchez Jacob Croft Jun Zhang CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier Journal of Personalized Medicine cerebral cavernous malformations CCM signaling complex blood-brain barrier tight junctions and adherens junction endothelial cells progesterone |
| title | CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier |
| title_full | CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier |
| title_fullStr | CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier |
| title_full_unstemmed | CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier |
| title_short | CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier |
| title_sort | cmpn cmp signaling networks in the maintenance of the blood vessel barrier |
| topic | cerebral cavernous malformations CCM signaling complex blood-brain barrier tight junctions and adherens junction endothelial cells progesterone |
| url | https://www.mdpi.com/2075-4426/13/5/751 |
| work_keys_str_mv | AT revathignanasekaran cmpncmpsignalingnetworksinthemaintenanceofthebloodvesselbarrier AT justinaickareth cmpncmpsignalingnetworksinthemaintenanceofthebloodvesselbarrier AT majdhawwar cmpncmpsignalingnetworksinthemaintenanceofthebloodvesselbarrier AT nickolassanchez cmpncmpsignalingnetworksinthemaintenanceofthebloodvesselbarrier AT jacobcroft cmpncmpsignalingnetworksinthemaintenanceofthebloodvesselbarrier AT junzhang cmpncmpsignalingnetworksinthemaintenanceofthebloodvesselbarrier |