Thrombin disrupts vascular endothelial-cadherin and leads to hydrocephalus via protease-activated receptors-1 pathway
| Autor: | Lu-Sha Tong, De-Sheng Shang, Xiao-di Hao, Feng Gao, Hong-Mei Zhang, Chen-Sheng Le |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Protein Serine-Threonine Kinases Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Thrombin Western blot Physiology (medical) Internal medicine medicine Animals Pharmacology (medical) Receptor Evans Blue Injections Intraventricular Pharmacology medicine.diagnostic_test Chemistry Cadherin Original Articles medicine.disease Cadherins Hydrocephalus Rats Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure Endocrinology Ventricle Choroid plexus Endothelium Vascular 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | CNS neurosciencetherapeutics. 25(10) |
| ISSN: | 1755-5949 |
| Popis: | Aims Previous studies indicated that intraventricular injection of thrombin would induce hydrocephalus. But how thrombin works in this process remains unclear. Since cadherin plays a critical role in hydrocephalus, we aimed to explore the mechanisms of how thrombin acted on choroid plexus vascular endothelium and how thrombin interacted with vascular endothelial-cadherin (VE-cadherin) during hydrocephalus. Methods There were two parts in this study. Firstly, rats received an injection of saline or thrombin into the right lateral ventricle. Magnetic resonance imaging was applied to measure the lateral ventricle volumes. Albumin leakage and Evans blue content were assessed to test the blood-brain barrier function. Immunofluorescence and Western blot were applied to detect the location and the expression of VE-cadherin. Secondly, we observed the roles of protease-activated receptors-1 (PAR1) inhibitor (SCH79797), Src inhibitor (PP2), p21-activated kinase-1 (PAK1) inhibitor (IPA3) in the thrombin-induced hydrocephalus, and their effects on the regulation of VE-cadherin. Results Our study demonstrated that intraventricular injection of thrombin caused significant downregulation of VE-cadherin in choroid plexus and dilation of ventricles. In addition, the inhibition of PAR1/p-Src/p-PAK1 pathway reversed the decrease of VE-cadherin and attenuated thrombin-induced hydrocephalus. Conclusions Our results suggested that the thrombin-induced hydrocephalus was associated with the inhibition of VE-cadherin via the PAR1/p-Src/p-PAK1 pathway. |
| Databáze: | OpenAIRE |
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