Role of PDGF-D and PDGFR-β in neuroinflammation in experimental ICH mice model
| Autor: | William J. Pearce, Peng Yang, gaiqing Wang, Andre Obenaus, Qin Hu, Gang Chen, Richard E. Hartman, Feng Xu, Anatol Manaenko, Liyan Miao, Zhen-Ni Guo, John H. Zhang, Xuezhen Hu, Jiping Tang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment Brain Edema Basal Ganglia Mice 0302 clinical medicine Neuroinflammation 2.1 Biological and endogenous factors Psychology Fibrinolysin Aetiology RNA Small Interfering Receptor Platelet-Derived Growth Factor biology Chemistry PDGF-D Platelet-Derived Growth Factor beta Neurology Aminocaproic Acid Imatinib Mesylate Encephalitis Tumor necrosis factor alpha Microglia medicine.symptom Platelet-derived growth factor receptor Agonist medicine.drug_class Clinical Sciences Inflammation Nerve Tissue Proteins Small Interfering PDGFR-β Article Receptor Platelet-Derived Growth Factor beta 03 medical and health sciences Developmental Neuroscience Growth factor receptor Fibrinolytic Agents medicine Animals cardiovascular diseases Protein Kinase Inhibitors Cerebral Hemorrhage ICH Neurology & Neurosurgery Animal Growth factor Macrophages Neurosciences Disease Models Animal 030104 developmental biology Gene Expression Regulation Immunology Disease Models biology.protein Cancer research Exploratory Behavior RNA 030217 neurology & neurosurgery PDGFR-beta |
| Zdroj: | Experimental neurology, vol 283, iss Pt A |
| ISSN: | 1090-2430 |
| Popis: | ObjectiveInflammation plays a key role in the pathophysiological processes after intracerebral hemorrhage (ICH). Post-ICH macrophages infiltrate the brain and release pro-inflammatory factors (tumor necrosis factor-α), amplifying microglial activation and neutrophil infiltration. Platelet-derived growth factor receptor-β (PDGFR-β) is expressed on macrophages and it's activation induces the recruitment of macrophages. Platelet-derived growth factor-D (PDGF-D) is an agonist with a significantly higher affinity to the PDGFR-β compared to another isoform of the receptor. In this study, we investigated the role of PDGF-D in the pro-inflammatory response after ICH in mice.MethodsA blood injection model of ICH was used in eight-week old male CD1 mice (weight 30g). Some mice received an injection of plasmin or PDGF-D. Gleevec, a PDGFR inhibitor, was administered at 1, 3 or 6h post-ICH. Plasmin was administered with or without PDGF-D siRNAs mixture or scramble siRNA. A plasmin-antagonist, ε-Aminocaproic acid (EACA), was co-administrated with the blood. The effects of ICH and treatment on the brain injury and post-ICH inflammation were investigated.ResultsICH resulted in the overexpression of PDGF-D, associated with the infiltration of macrophages. PDGFR-inhibition decreased ICH-induced brain injury, attenuating macrophage and neutrophil infiltration, reducing microglial activation and TNF-α production. Administration of recombinant PDGF-D induced TNF-α production, and PDGFR-inhibition attenuated it. A plasmin-antagonist suppressed PDGFR-β activation and microglial activation. Plasmin increased PDGF-D expression, and PDGF-D inhibition reduced neutrophil infiltration.ConclusionICH-induced PDGF-D accumulation contributed to post-ICH inflammation via PDGFR activation and enhanced macrophage infiltration. The inhibition of PDGFR had an anti-inflammatory effect. Plasmin is a possible upstream effector of PDGF-D. The targeting of PDGF-D may provide a novel way to decrease brain injury after ICH. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect