PMID- 33479232 OWN - NLM STAT- MEDLINE DCOM- 20211005 LR - 20230128 IS - 2041-4889 (Electronic) VI - 12 IP - 1 DP - 2021 Jan 21 TI - Acidic fibroblast growth factor attenuates type 2 diabetes-induced demyelination via suppressing oxidative stress damage. PG - 107 LID - 10.1038/s41419-021-03407-2 [doi] LID - 107 AB - Prolonged type 2 diabetes mellitus (T2DM) produces a common complication, peripheral neuropathy, which is accompanied by nerve fiber disorder, axon atrophy, and demyelination. Growing evidence has characterized the beneficial effects of acidic fibroblast growth factor (aFGF) and shown that it relieves hyperglycemia, increases insulin sensitivity, and ameliorates neuropathic impairment. However, there is scarce evidence on the role of aFGF on remodeling of aberrant myelin under hyperglycemia condition. Presently, we observed that the expression of aFGF was rapidly decreased in a db/db T2DM mouse model. Administration of exogenous aFGF was sufficient to block acute demyelination and nerve fiber disorganization. Furthermore, this strong anti-demyelinating effect was most likely dominated by an aFGF-mediated increase of Schwann cell (SC) proliferation and migration as well as suppression of its apoptosis. Mechanistically, the beneficial biological effects of aFGF on SC behavior and abnormal myelin morphology were likely due to the inhibition of hyperglycemia-induced oxidative stress activation, which was most likely activated by kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-derived-like 2 (Nrf2) signaling. Thus, this evidence indicates that aFGF is a promising protective agent for relieving myelin pathology through countering oxidative stress signaling cascades under diabetic conditions. FAU - Li, Rui AU - Li R AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. AD - Research Center, Affiliated Xiangshang Hospital, Wenzhou Medical University, 315700, Ningbo, Zhejiang, China. AD - School of Chemistry, Sun Yat-sen University, 510275, Guangzhou, Guangdong, China. FAU - Wang, Beini AU - Wang B AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Wu, Chengbiao AU - Wu C AD - Research Center, Affiliated Xiangshang Hospital, Wenzhou Medical University, 315700, Ningbo, Zhejiang, China. FAU - Li, Duohui AU - Li D AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Wu, Yanqing AU - Wu Y AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Ye, Libing AU - Ye L AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Ye, Luxia AU - Ye L AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Chen, Xiongjian AU - Chen X AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Li, Peifeng AU - Li P AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Yuan, Yuan AU - Yuan Y AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Zhang, Hongyu AU - Zhang H AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Xie, Ling AU - Xie L AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Li, Xiaokun AU - Li X AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. FAU - Xiao, Jian AU - Xiao J AUID- ORCID: 0000-0001-7374-6506 AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. xfxj2000@126.com. FAU - Wang, Jian AU - Wang J AD - Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China. jianwang0516@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210121 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Reactive Oxygen Species) RN - 104781-85-3 (Fibroblast Growth Factor 1) SB - IM MH - Animals MH - Diabetes Mellitus, Type 2/*therapy MH - Disease Models, Animal MH - Fibroblast Growth Factor 1/pharmacology/*therapeutic use MH - Male MH - Mice MH - Oxidative Stress MH - Rats MH - Reactive Oxygen Species PMC - PMC7819983 COIS- The authors declare that they have no conflict of interest. EDAT- 2021/01/23 06:00 MHDA- 2021/10/06 06:00 PMCR- 2021/01/21 CRDT- 2021/01/22 06:18 PHST- 2020/08/21 00:00 [received] PHST- 2020/12/17 00:00 [accepted] PHST- 2020/12/16 00:00 [revised] PHST- 2021/01/22 06:18 [entrez] PHST- 2021/01/23 06:00 [pubmed] PHST- 2021/10/06 06:00 [medline] PHST- 2021/01/21 00:00 [pmc-release] AID - 10.1038/s41419-021-03407-2 [pii] AID - 3407 [pii] AID - 10.1038/s41419-021-03407-2 [doi] PST - epublish SO - Cell Death Dis. 2021 Jan 21;12(1):107. doi: 10.1038/s41419-021-03407-2.