title: IL-1β-induces NF-κB and upregulates microRNA-372 to inhibit spinal cord injury recovery.
abstract: Excessive inflammation including IL-1β-initiated signaling is among the earlies reactions that can cause neuronal damage following spinal cord injury (SCI). It has been suggested that microRNAs may participate in stem cell repair to facilitate functional recovery following SCI. In this study we have shown that in cultured human neural stem cells (hNSC), IL-1β reduced the expression of both KIF3B (kinesin family member 3B) and NOSIP (nitric oxide synthase-interacting protein), two key modulators for restricting inflammation and promoting neuronal regeneration. The induction of microRNA-372 (miR-372) by IL-1β is specifically responsible for the inhibition of KIF3B and NOSIP. The 3'-untranslated regions (UTRs) of both KIF3B and NOSIP contain targeting sequences to miR-372 that directly inhibit their expression. Moreover, we found that the expression of miR-372 was stimulated in hNSC by IL-1β through an NF-κB binding site at its promoter region. Finally, stable overexpression of miR-372 inhibitor in hNSC rescued the IL-1β-induced impairment as shown by significant improvements in tissue water content, myeloperoxidase activity, and behavioral assessments in SCI rats. These findings suggest a critical role of miR-372 in inflammatory signaling and pinpoint a novel target for the treatment of acute SCI.NEW & NOTEWORTHYOur data demonstrate that IL-1β can impair the functional recovery of neural stem cell transplant therapy for spinal cord injury (SCI) treatment in rats. This effect is dependent on microRNA-372 (miR-372)-dependent gene repression of KIF3B and NOSIP. Therefore, specific knockdown of miR-372 may provide benefits for SCI treatments.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, People's Republic of China.|Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China; and.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Tongzhou
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China; and.
authors.forename: Youshui
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China; and.
authors.forename: Peipei
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China; and.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China; and.
authors.forename: Chenhao
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China; and.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, People's Republic of China; yuxw@sjtu.edu.cn.|Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China; and.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D053583:Interleukin-1beta; C095899:KIF3B protein, human; C561021:MIRN372 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C419706:NOSIP protein, human; D044767:Ubiquitin-Protein Ligases; D016547:Kinesins
keywords: KIF3B; NOSIP; microRNA; neural stem cell; spinal cord injury