Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor-beta2.
The transforming growth factor-betas (TGF-betas) are potent fibrogenic factors implicated in numerous central nervous system (CNS) pathologies in which fibrosis and neural dysfunction are causally associated. In this study, we aim to limit the fibrogenic process in a model of CNS scarring using a recombinant human monoclonal antibody, derived from phage display libraries and specific to the active form of the TGF-beta2 isoform. The implicit inference of the work was that, as such antibodies are potential pharmacological agents for the treatment of human CNS fibrotic diseases, validation of efficacy in a mammalian animal model is a first step towards this end. Treatment of cerebral wounds with the anti-TGF-beta2 antibody led to a marked attenuation of all aspects of CNS scarring, including matrix deposition, formation of an accessory glial-limiting membrane, inflammation and angiogenesis. For example, in the wound, levels of: (i) the connective tissue components fibronectin, laminin and chondroitin sulphate proteoglycan; and (ii) wound-responsive cells including astrocytes and macrophages/microglia, were markedly reduced. Our findings suggest that such synthetic anti-fibrotic TGF-beta antibodies are potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components, and maintain and/or restore functional integrity.
Logan
A
A
Department of Medicine, University of Birmingham, UK. a.logan@bham.ac.uk
Green
J
J
Hunter
A
A
Jackson
R
R
Berry
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D001930:Brain Injuries / Q000150:complications*; D002921:Cicatrix / Q000473:pathology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D009457:Neuroglia / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000276:immunology*; D014950:Wounds, Penetrating / Q000150:complications*
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta