title: Increased mRNA expression of tissue inhibitors of metalloproteinase-1 and -2 in Duchenne muscular dystrophy.
abstract: In dystrophinopathies, disease severity is generally related to the extent of muscle fibrosis. To determine whether a decrease in matrix degradation contributes to the severe fibrosis seen in Duchenne muscular dystrophy (DMD), we quantified RNA transcript numbers for the fibrolytic matrix metalloproteinases (MMP)-1 and -2 and their natural tissue inhibitors (TIMP)-1 and -2 in DMD muscle as well as in pathological and normal controls. In addition, we investigated gelatinase (MMP-2) enzyme activity by zymography. We found an up-regulation of TIMP-1, TIMP-2 and MMP-2 RNA in DMD muscle. Zymography revealed an increase in MMP-2 activity in DMD muscle homogenates, which was absent in pathological and normal controls. Therefore, besides enhanced fibrogenesis, a disturbance of matrix degradation may play a significant role in muscle fibrosis in DMD. TIMP-1 should be investigated further as a promising target for pharmacological intervention to prevent muscle fibrosis in DMD.
authors.affiliation: Department of Neuropediatrics, Charité, University Medical Center Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. arpad.von_moers@charite.de
authors.forename: Arpad
authors.initials: A
authors.lastname: von Moers
authors.forename: Angelika
authors.initials: A
authors.lastname: Zwirner
authors.forename: Anke
authors.initials: A
authors.lastname: Reinhold
authors.forename: Olaf
authors.initials: O
authors.lastname: Brückmann
authors.forename: Frank
authors.initials: F
authors.lastname: van Landeghem
authors.forename: Gisela
authors.initials: G
authors.lastname: Stoltenburg-Didinger
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Herrman
authors.initials: H
authors.lastname: Herbst
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D020388:Muscular Dystrophy, Duchenne / Q000201:enzymology* / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016372:RNA, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D014746:Vimentin / Q000378:metabolism
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016372:RNA, Antisense; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014746:Vimentin; D019716:Tissue Inhibitor of Metalloproteinase-2