The Journal of Biological Chemistry ADAMTSL6β rescues disorder in Marfan syndrome Saito et al, Page1 ADAMTSL6β rescues fibrillin-1 microfibril disorder in a Marfan syndrome mouse model through the promotion of fibrillin-1 assembly

Marfan’s syndrome (MFS) is a systemic disorder of the connective tissues caused by insufficient fibrillin-1 microfibril formation and can cause cardiac complications, emphysema, ocular lens dislocation and severe periodontal disease. A disintegrinlike metalloprotease domain with thrombospondin type I motifs like (ADAMTSL) 6β is a microfibril-associated extracellular matrix protein expressed in various connective tissues that has been implicated in fibrillin-1 microfibril assembly. We here report that ADAMTSL6β plays an essential role in the development and regeneration of connective tissues. ADAMTSL6β expression rescues microfibril disorder after periodontal ligament (PDL) injury in an MFS mouse model through the promotion of fibrillin-1 microfibril assembly. In addition, improved fibrillin-1 assembly in MFS mice following the administration of ADAMTSL6β attenuates the over-activation of TGF-β signals associated with the increased release of active TGF-β from disrupted fibrillin-1 microfibrils within PDLs. Our current data thus demonstrate the essential contribution of ADAMTSL6β to fibrillin-1 microfibril formation. These findings also suggest a new therapeutic strategy for the treatment of MFS through ADAMTSL6β-mediated fibrillin-1 microfibril assembly. http://www.jbc.org/cgi/doi/10.1074/jbc.M111.243451 The latest version is at JBC Papers in Press. Published on August 31, 2011 as Manuscript M111.243451 Copyright 2011 by The American Society for Biochemistry and Molecular Biology, Inc. by gest on Jne 8, 2017 hp://w w w .jb.org/ D ow nladed from The Journal of Biological Chemistry ADAMTSL6β rescues disorder in Marfan syndrome