PMID- 35579787 OWN - NLM STAT- MEDLINE DCOM- 20220718 LR - 20220727 IS - 1573-7365 (Electronic) IS - 0885-7490 (Linking) VI - 37 IP - 6 DP - 2022 Aug TI - NGF/TrkA promotes the vitality, migration and adhesion of bone marrow stromal cells in hypoxia by regulating the Nrf2 pathway. PG - 2017-2026 LID - 10.1007/s11011-022-00974-x [doi] AB - BACKGROUND: Bone marrow stromal cells (BMSCs) transplantation is a treatment strategy for ischemic stroke (IS) with great potential. However, the vitality, migration and adhesion of BMSCs are greatly impaired due to the harsh environment of the ischemic area, which affects the therapeutic effects. Herein, we aimed to investigate the roles of nerve growth factor (NGF) in regulating cell behaviors of BMSCs in IS. METHODS: The mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. To simulate ischemic-like conditions in vitro, Brain microvascular (bEnd.3) cells were exposed to oxygen and glucose deprivation (OGD). Cell viability and cell proliferation were evaluated by MTT assay and BrdU assay, respectively. Transwell migration and cell adhesion assays were carried out to determine cell migration and adhesion of BMSCs, respectively, coupled with flow cytometry to evaluate cell apoptosis of bEnd.3 cells. Finally, angiogenesis assay was performed to assess the angiogenesis ability of bEnd.3 cells. RESULTS: NGF overexpression resulted in increased cell vitality, adhesion and migration of BMSCs, while NGF knockdown presented the opposite effects. We subsequently discovered that TrkA was a receptor for NGF, and TrkA knockdown significantly inhibited the cell viability, migration and adhesion of BMSCs. Besides, Nrf2 was confirmed as the downstream target of NGF/TrkA to promote the viability, adhesion and migration of BMSC cells. Finally, NGF-silenced BMSCs could not effectively restore the OGD-induced brain microvascular cell damage. CONCLUSIONS: NGF/TrkA promoted the viability, migration and adhesion of BMSCs in IS via activating Nrf2 pathway. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Fang, Cui-Ni AU - Fang CN AD - Department of Rehabilitation, Hunan Provincial People's Hospital (the first-affiliated Hospital of Hunan normal University), No.89, Guhan Road, Furong District, 410000, Changsha, Hunan Province, P.R. China. FAU - Tan, Hai-Qun AU - Tan HQ AD - Department of Rehabilitation, Hunan Provincial People's Hospital (the first-affiliated Hospital of Hunan normal University), No.89, Guhan Road, Furong District, 410000, Changsha, Hunan Province, P.R. China. FAU - Song, Ao-Bo AU - Song AB AD - Department of Rehabilitation, Hunan Provincial People's Hospital (the first-affiliated Hospital of Hunan normal University), No.89, Guhan Road, Furong District, 410000, Changsha, Hunan Province, P.R. China. FAU - Jiang, Ni AU - Jiang N AD - Department of Rehabilitation, Hunan Provincial People's Hospital (the first-affiliated Hospital of Hunan normal University), No.89, Guhan Road, Furong District, 410000, Changsha, Hunan Province, P.R. China. FAU - Liu, Qian-Rong AU - Liu QR AD - Department of Rehabilitation, Hunan Provincial People's Hospital (the first-affiliated Hospital of Hunan normal University), No.89, Guhan Road, Furong District, 410000, Changsha, Hunan Province, P.R. China. FAU - Song, Tao AU - Song T AUID- ORCID: 0000-0002-3259-2456 AD - Department of Rehabilitation, Hunan Provincial People's Hospital (the first-affiliated Hospital of Hunan normal University), No.89, Guhan Road, Furong District, 410000, Changsha, Hunan Province, P.R. China. songtao0731@126.com. LA - eng PT - Journal Article DEP - 20220517 PL - United States TA - Metab Brain Dis JT - Metabolic brain disease JID - 8610370 RN - 0 (NF-E2-Related Factor 2) RN - 0 (NTRK1 protein, human) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor, trkA) SB - IM MH - Animals MH - Bone Marrow Cells/metabolism MH - Cells, Cultured MH - Endothelial Cells/metabolism MH - Humans MH - Hypoxia MH - *Mesenchymal Stem Cells/metabolism MH - Mice MH - NF-E2-Related Factor 2/metabolism MH - *Nerve Growth Factor/metabolism MH - Receptor, trkA OTO - NOTNLM OT - Bone marrow stromal cells OT - Cell adhesion OT - Cell migration OT - Ischemic stroke OT - NGF/TrkA EDAT- 2022/05/18 06:00 MHDA- 2022/07/19 06:00 CRDT- 2022/05/17 11:18 PHST- 2021/11/09 00:00 [received] PHST- 2022/03/24 00:00 [accepted] PHST- 2022/05/18 06:00 [pubmed] PHST- 2022/07/19 06:00 [medline] PHST- 2022/05/17 11:18 [entrez] AID - 10.1007/s11011-022-00974-x [pii] AID - 10.1007/s11011-022-00974-x [doi] PST - ppublish SO - Metab Brain Dis. 2022 Aug;37(6):2017-2026. doi: 10.1007/s11011-022-00974-x. Epub 2022 May 17.