期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2019.00328
关键词
basic fiboblast growth factor; astrocyte; proliferation; amyloid beta; Cyclin D1
资金
- National Natural Science Foundation of China [81703492, 81774006]
- Beijing Municipal Natural Science Foundation [7182092]
- Minzu University Research Fund [2018CXTD03]
- MUC 111 project
- Canadian Institutes for Health Research [FRN-74733]
- Intramural Research Program of the Eunice Kennedy Shriver National Institute of Health and Human Development, National Institutes of Health, USA
Astrocytes are the most abundant type of glial cells in the brain, and they play a key role in Alzheimer's disease (AD). Fibroblast Growth Factor-2 (FGF-2) has been implicated as a potential therapeutic agent for treating AD. In the present study, we investigated the protective effects of low molecular weight (LMW; 17 KDa) and high molecular weight (HMW; 23 KDa) forms of FGF-2 on A beta(1-42)-induced toxicity, and proliferation in astrocytes. We show that both isoforms of FGF-2 have similar protective effects against A beta(1-42)-induced cytotoxicity in primary cultured cortical astrocytes as measured by Lactate Dehydrogenase (LDH) release assay. Additionally, 17 KDa FGF-2 significantly promoted astrocyte proliferation as measured by Trypan Blue, DRAQ5 and 5-ethynyl-2'-deoxyuridine (EdU) staining, but not 23 kDa FGF-2. Furthermore, our results demonstrated that AKT signaling pathway was required for the protective and proliferative effects of FGF-2. Downstream effector studies indicated that 17 kDa FGF-2 promoted astrocyte proliferation by enhanced expression of c-Myc, Cyclin D1, Cyclin E. Furthermore, our data suggested that Cyclin D1 was required for the proliferative effect of LMW FGF2 in astrocytes. Taken together, our findings provide important information for the similarities and differences between 23 kDa and17 kDa isoforms of FGF-2 on astrocyte survival and proliferation.
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