Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage
| Autor: | Kaijie Wang, Huaxin Sheng, Yanxia Tian, Junling Gao, Changmeng Cui, Jianzhong Cui, Xiaohua Jiang, Ran Li, Ying Cui |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pathology Physiology Stem cells lcsh:Physiology Rats Sprague-Dawley Phosphatidylinositol 3-Kinases GAP-43 Protein 0302 clinical medicine Medicine lcsh:QD415-436 Cells Cultured Phosphoinositide-3 Kinase Inhibitors Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 lcsh:QP1-981 Neuroprotection Up-Regulation medicine.anatomical_structure Stem cell Axonal regeneration Signal Transduction medicine.medical_specialty Morpholines Bone Marrow Cells Mesenchymal Stem Cell Transplantation lcsh:Biochemistry 03 medical and health sciences Animals Regeneration Protein kinase B PI3K/AKT/mTOR pathway Cerebral Hemorrhage Flavonoids Intracerebral hemorrhage business.industry Mesenchymal stem cell Mesenchymal Stem Cells medicine.disease Axons Rats Transplantation Disease Models Animal 030104 developmental biology Chromones Bone marrow business Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 42, Iss 1, Pp 137-144 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Intracerebral hemorrhage (ICH) occurs in hypertensive patients and results in high rates of mortality and disability. This study determined whether bone marrow mesenchymal stem cell (BMSC) transplantation affects axonal regeneration and examined the underlying mechanisms after the administration of PD98059 (p-ERK1/2 inhibitor) or/ and LY294002 (PI3K inhibitor). The hypothesis that was intended to be tested was that BMSC transplantation regulates the expression of growth-associated protein-43 (GAP-43) via the ERK1/2 and PI3K/Akt signaling pathways. Methods: Seventy-five male rats (250–280 g) were subjected to intracerebral blood injection and then randomly received a vehicle, BMSCs, PD98059 or LY294002 treatment. Neurological deficits were evaluated prior to injury and at 1, 3 and 7 days post-injury. The expression of GAP-43, Akt, p-Akt, ERK1/2, and p-ERK1/2 proteins was measured by western blot analysis. Results: BMSC transplantation attenuated neurological deficits 3-7 days post-ICH. The expression of GAP-43 was increased 3 days following BMSC transplantation. However, this increase was inhibited by either PD98059 or LY294002 treatment. Treatment with both PD98059 and LY294002 was more effective than was treatment with an individual compound. Conclusion: BMSC transplantation could attenuate neurological deficits and activate axonal regeneration in this rat ICH model. The protective effects might be associated with increased GAP-43 expression by activating both the ERK1/2 and PI3K/Akt signaling pathways. |
| Databáze: | OpenAIRE |
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