title: Downregulation of the Long Non-Coding RNA Meg3 Promotes Angiogenesis After Ischemic Brain Injury by Activating Notch Signaling.
abstract: Angiogenesis after ischemic brain injury contributes to the restoration of blood supply in the ischemic zone. Strategies to improve angiogenesis may facilitate the function recovery after stroke. Recent researches have demonstrated that dysfunction of long non-coding RNAs are associated with angiogenesis. We have previously reported that long non-coding RNAs (lncRNAs) are aberrantly expressed in ischemic stroke. However, little is known about long non-coding RNAs and theirs role in angiogenesis after stroke. In this study, we identified a rat lncRNAs, Meg3, and found that Meg3 was significantly decreased after ischemic stroke. Overexpression of Meg3 suppressed functional recovery and decreased capillary density after ischemic stroke. Downregulation of Meg3 ameliorated brain lesion and increased angiogenesis after ischemic stroke. Silencing of Meg3 resulted in a proangiogenic effect evidenced by increased endothelial cell migration, proliferation, sprouting, and tube formation. Mechanistically, we showed that Meg3 negatively regulated notch pathway both in vivo and in vitro. Inhibition of notch signaling in endothelial cells reversed the proangiogenic effect induced by Meg3 downregulation. This study revealed the function of Meg3 in ischemic stroke and elucidated its mechanism in angiogenesis after ischemic stroke.
authors.affiliation: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. liqing_236@aliyun.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Kun-Shan
authors.initials: KS
authors.lastname: Zhang
authors.affiliation: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Niu
authors.affiliation: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Zhou
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Si-Guang
authors.initials: SG
authors.lastname: Li
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Luo
authors.affiliation: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. wangy63cn@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. dengzf63@126.com.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Deng
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000502:physiology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020521:Stroke / Q000378:metabolism / Q000473:pathology
chemical_list: C000621783:MEG3 non-coding RNA, rat; D062085:RNA, Long Noncoding; D051880:Receptors, Notch
keywords: Angiogenesis; Ischemic stroke; LncRNAs; MEG3; Notch pathway