Protective Role of SOCS3 Modified Bone Marrow Mesenchymal Stem Cells in Hypoxia-Induced Injury of PC12 Cells
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.
KeywordsSOCS3 BMSCs JAK/STAT3 Hypoxia PC12 cells
We thank the reviewers for their insightful suggestions and comments.
Compliance with Ethical Standards
This study has got the approval from the Ethics Committee for Animal Experiments in Linyi Central Hospital, which was in strictly obedience to the Guide for the Care and Use of Laboratory Animals published by the National Institute of Health in the USA (Health 1985).
Conflicts of Interest
The authors declare that they have no conflict of interest.
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