title: Critical role of regulator of calcineurin 1 in spinal cord injury.
abstract: Spinal cord injury (SCI) is a severe clinical problem worldwide. The pathogenesis of SCI is complicated and much is unknown. The current study was designed to investigate the possible role of regulator of calcineurin 1 (RCAN1) in SCI and to explore the possible molecular mechanisms. Rats were injected with LVshRNAi-RCAN1 and then contusion-induced SCI was established. We found that RCAN1 was significantly increased in spinal cord of rats with SCI. Knockdown of RCAN1 markedly facilitated the structural and functional recovery in the spinal cord, as illustrated by decrease of lesion volume and increase of Basso, Beattie, and Bresnahan (BBB) and combined behavioral score (CBS) scores. Downregulation of RCAN1 suppressed the increase of pro-inflammatory cytokines, including IL-1β and TNF-α, and inhibited the increase of TUNEL-positive cell numbers and caspases 3 and 9 activities. The decrease of oxygen consumption rate and increase of expression of glucose-regulated protein 78 (GRP78) and phosphorylation of protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) in rats with SCI were inhibited by LVshRNAi-RCAN1. Moreover, knockdown of RCAN1 ameliorated oxidative stress in rats with SCI, as evidenced by decrease of TBA reactive substances (TBARS) and GSSG content and increase of glutathione (GSH) level. These results suggested that RCAN1 played an important role in SCI through regulation of various pathological processes. Overall, the data provide novel insights into the role of RCAN1 in SCI and novel therapeutic targets of the treatment of injury in the spinal cord.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People's Republic of China. guodong_wang02@163.com.
authors.forename: Guodong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People's Republic of China.
authors.forename: Yilei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People's Republic of China.
authors.forename: Shenpeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People's Republic of China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People's Republic of China.
authors.forename: Tan
authors.initials: T
authors.lastname: Lu
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione; D006360:Heat-Shock Proteins; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D019892:eIF-2 Kinase; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C000594089:IL1B protein, rat; C548050:RCAN1 protein, rat; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat
keywords: Apoptosis; Inflammation; Oxidative stress; Regulator of calcineurin 1; Spinal cord injury