title: Anti-apoptotic effect of microRNA-21 after contusion spinal cord injury in rats.
abstract: Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). Dysregulation of microRNAs (miRNAs) has been found following SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. We analyzed the miRNA expression patterns 1 and 3 days following rat SCI using miRNA microarray. Microarray data revealed that nine miRNAs were upregulated and five miRNAs were downregulated 1 day post-injury, and that three miRNAs were upregulated and five miRNAs were downregulated 3 days post-injury, in the sites of contused when compared with sham rat spinal cords. Because miR-21 was one of the miRNAs being most significantly upregulated, we investigated its function. Knockdown of miR-21 by antagomir-21 led to attenuated recovery in hindlimb motor function, increased lesion size, and decreased tissue sparing in rats. Compared with the negative control group, treatment with antagomir-21 significantly increased apoptosis following SCI. Pro-apoptosis genes Fas ligand (FasL), phosphatase and tensin homolog (PTEN), and programmed cell death protein 4 (PDCD4) were proved to be direct targets of miR-21 in many diseases and cell types. In vivo treatment with antagomir-21 increased the expression of FasL and PTEN, but did not affect PDCD4. These results suggested that miR-21 played an important role in limiting secondary cell death following SCI, and that the protective effects of miR-21 might have been the result of its regulation on pro-apoptotic genes. Thus, miR-21 may play an important role in the pathophysiology of SCI.
authors: Department of Spine Surgery, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
authors: Jian-Zhong
authors: JZ
authors: Hu
authors: Jiang-Hu
authors: JH
authors: Huang
authors: Lei
authors: L
authors: Zeng
authors: Guan
authors: G
authors: Wang
authors: Min
authors: M
authors: Cao
authors: Hong-Bin
authors: HB
authors: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D035683:MicroRNAs; C546082:mirn21 microRNA, rat
references: Neurobiol Dis. 2008 Mar;29(3):438-45
references: 18082412
references: Spine (Phila Pa 1976). 2004 Jul 1;29(13):1394-404
references: 15223929
references: PLoS One. 2012;7(4):e34534
references: 22511948
references: Circ Res. 2007 Jun 8;100(11):1579-88
references: 17478730
references: Kidney Int. 2012 Dec;82(11):1167-75
references: 22785173
references: FEBS Lett. 2007 Feb 6;581(3):495-505
references: 17239858
references: Glia. 2012 Dec;60(12):1888-95
references: 22907769
references: Oncogene. 2008 Apr 3;27(15):2128-36
references: 17968323
references: Cardiovasc Res. 2010 Aug 1;87(3):431-9
references: 20219857
references: J Neurotrauma. 1995 Feb;12(1):1-21
references: 7783230
references: Mol Carcinog. 2013 Apr;52(4):286-96
references: 22213145
references: J Biol Chem. 2010 Jun 25;285(26):20281-90
references: 20404348
references: Brain Res Brain Res Rev. 2004 Jan;44(1):65-81
references: 14739003
references: Nat Med. 2004 Apr;10(4):389-95
references: 15004554
references: Genome Res. 2009 Jan;19(1):92-105
references: 18955434
references: J Neurosci Res. 2009 May 1;87(6):1435-48
references: 19021292
references: Exp Neurol. 2009 Oct;219(2):424-9
references: 19576215
references: Clin Neuropharmacol. 2001 Sep-Oct;24(5):254-64
references: 11586110
references: FEBS J. 2010 Oct;277(20):4299-307
references: 20840605
references: Nat Rev Neurosci. 2006 Dec;7(12):911-20
references: 17115073
references: J Neurochem. 2010 Mar;112(6):1500-12
references: 20050973
references: J Biol Chem. 2009 Oct 23;284(43):29514-25
references: 19706597
references: Brain Res. 2009 Aug 11;1284:191-201
references: 19501075
references: Neuroscience. 2001;103(1):203-18
references: 11311801
references: Neuroscience. 2011 Jul 14;186:146-60
references: 21513774
references: Physiol Genomics. 2005 Aug 11;22(3):368-81
references: 15942019
references: Nat Rev Neurosci. 2006 Aug;7(8):628-43
references: 16858391
references: J Biol Chem. 2008 Jan 11;283(2):1026-33
references: 17991735
references: Biochem Biophys Res Commun. 2011 Jan 28;404(4):941-5
references: 21185267
references: Genes Chromosomes Cancer. 2008 Jun;47(6):530-42
references: 18335499
references: Oncogene. 2006 Oct 5;25(45):6101-12
references: 16682950
references: Cancer Res. 2005 Jul 15;65(14):6029-33
references: 16024602
references: Ann Neurol. 2003 Apr;53(4):454-68
references: 12666113
references: J Neurosci Res. 2011 Feb;89(2):212-21
references: 21162128
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: Gastroenterology. 2006 Jun;130(7):2113-29
references: 16762633
references: Nature. 2008 Sep 4;455(7209):64-71
references: 18668037
references: Spine J. 2002 Mar-Apr;2(2):116-28
references: 14588270
references: RNA. 2008 Mar;14(3):432-44
references: 18230762
references: J Neurotrauma. 2005 Feb;22(2):226-39
references: 15716629
references: Cancer Lett. 2008 Dec 18;272(2):197-205
references: 19013014