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Protective Role of SOCS3 Modified Bone Marrow Mesenchymal Stem Cells in Hypoxia-Induced Injury of PC12 Cells.
- Source :
-
Journal of molecular neuroscience : MN [J Mol Neurosci] 2019 Mar; Vol. 67 (3), pp. 400-410. Date of Electronic Publication: 2019 Jan 15. - Publication Year :
- 2019
-
Abstract
- We attempted to explore the possible effects of SOCS3 (suppressor of cytokine signaling 3)-modified bone marrow mesenchymal stem cells (BMSCs) on the hypoxic injury of rat adrenal gland pheochromocytoma (PC-12) cells. PC12 cells were cultured with EGFP (enhanced green fluorescent protein)-BMSCs and SOCS3-BMSCs respectively under hypoxia in vitro and classified into control, hypoxia, EGFP-BMSCs, and SOCS3-BMSC groups. CCK-8, Hoechst 33258 staining, and Annexin V-FITC/PI staining were assessed to measure the viability and apoptosis of hypoxia-induced PC12 cells. The JAK/STAT3 pathway- and apoptosis-related proteins were identified by Western blot. Finally, rat models of permanent middle cerebral artery occlusion (pMCAO) were established to verify the potential influences of SOCS3-BMSCs in vivo. SOCS3-modified BMSCs can stably express SOCS3 protein. EGFP-BMSCs, especially SOCS3-BMSCs, can improve cell viability and SOD content, and reduce cell apoptosis, LDH viability, and MDA content in hypoxia-induced PC12 cells (all P < 0.05). Besides, EGFP-BMSCs and SOCS3-BMSCs decreased cleaved caspase-3 level and increased Bcl-2/Bax of hypoxia-induced PC12 cells, while SOCS3-BMSCs could also elevate SOCS3 protein and reduce p-STAT3 protein level in hypoxia-induced PC12 cells (all P < 0.05). In vivo experiments confirmed that EGFP-BMSCs, particularly SOCS3-BMSCs, could ameliorate infarct size and inhibit neuronal apoptosis of different degrees in pMACO rats (all P < 0.05). SOCS3-modified BMSCs can alleviate oxidative stress, improve cell viability, and reduce neuronal apoptosis by downregulation of JAK/STAT3 pathway, thereby exerting the neuroprotective role in ischemic brain injury.
- Subjects :
- Animals
Cell Hypoxia
Cells, Cultured
Infarction, Middle Cerebral Artery therapy
Janus Kinases metabolism
Male
PC12 Cells
Rats
Rats, Sprague-Dawley
STAT3 Transcription Factor metabolism
Superoxide Dismutase metabolism
Suppressor of Cytokine Signaling 3 Protein genetics
Apoptosis
Infarction, Middle Cerebral Artery metabolism
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells metabolism
Suppressor of Cytokine Signaling 3 Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1166
- Volume :
- 67
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of molecular neuroscience : MN
- Publication Type :
- Academic Journal
- Accession number :
- 30648230
- Full Text :
- https://doi.org/10.1007/s12031-018-1243-7