PMID- 28415697 OWN - NLM STAT- MEDLINE DCOM- 20180305 LR - 20181113 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 17 DP - 2017 Apr 25 TI - Down-regulation of interleukin 7 receptor (IL-7R) contributes to central nervous system demyelination. PG - 28395-28407 LID - 10.18632/oncotarget.16081 [doi] AB - Interleukin 7 receptor (IL-7R) has been associated with the pathogenesis of multiple sclerosis (MS), though the mechanisms are not clear. Because myelin expression is highly conserved between zebrafish and mammals, zebrafish have become an ideal model for studying demyelination. We used a transgenic (Tg; mbp:nfsB-egfp) zebrafish line in which oligodendrocytes expressed green fluorescent protein (GFP) from the larval stage to adulthood. Exposing adult transgenic zebrafish to metronidazole induced demyelination that resembled the morphological changes associated with the early stages of MS. The metronidazole-induced demyelination was confirmed by magnetic resonance imaging (MRI) for the first time. Microarray analysis revealed down-regulation of IL-7R during demyelination. Targeted knockdown of IL-7R demonstrated that IL-7R is essential for myelination in embryonic and larval zebrafish. Moreover, IL-7R down-regulation induced signaling via the JAK/STAT pathway leading to apoptosis in oligodendrocytes. These findings contribute to our understanding of the role of IL-7R in demyelination, and provide a rationale for the development of IL-7R-based therapies for MS and other demyelinating diseases. FAU - Lei, Xudan AU - Lei X AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China. FAU - Cai, Shijiao AU - Cai S AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China. FAU - Chen, Yang AU - Chen Y AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China. FAU - Cui, Jianlin AU - Cui J AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China. FAU - Wang, Yajie AU - Wang Y AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China. FAU - Li, Zongjin AU - Li Z AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China. FAU - Li, Yuhao AU - Li Y AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Receptors, Interleukin-7) RN - 0 (STAT Transcription Factors) RN - EC 2.7.10.2 (Janus Kinases) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Central Nervous System Diseases/diagnostic imaging/*genetics/metabolism/pathology MH - Demyelinating Diseases/diagnostic imaging/*genetics/metabolism/pathology MH - Disease Models, Animal MH - Down-Regulation MH - Gene Expression Profiling MH - *Gene Expression Regulation MH - Gene Knockdown Techniques MH - Genes, bcl-2 MH - Janus Kinases/metabolism MH - Receptors, Interleukin-7/*genetics/metabolism MH - STAT Transcription Factors/metabolism MH - Signal Transduction MH - Spinal Cord/metabolism/pathology MH - Zebrafish PMC - PMC5438658 OTO - NOTNLM OT - demyelination OT - interleukin 7 receptor (IL-7R) OT - myelin basic protein OT - myelination OT - zebrafish COIS- CONFLICTS OF INTEREST The authors declare no competing financial interests. EDAT- 2017/04/19 06:00 MHDA- 2018/03/06 06:00 PMCR- 2017/04/25 CRDT- 2017/04/19 06:00 PHST- 2016/11/08 00:00 [received] PHST- 2017/02/27 00:00 [accepted] PHST- 2017/04/19 06:00 [pubmed] PHST- 2018/03/06 06:00 [medline] PHST- 2017/04/19 06:00 [entrez] PHST- 2017/04/25 00:00 [pmc-release] AID - 16081 [pii] AID - 10.18632/oncotarget.16081 [doi] PST - ppublish SO - Oncotarget. 2017 Apr 25;8(17):28395-28407. doi: 10.18632/oncotarget.16081.