ADAMTSL6? protein rescues fibrillin-1 microfibril disorder in a Marfan syndrome mouse model through the promotion of fibrillin-1 assembly.

ABSTRACT: Marfan 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. ADAMTSL6? (A disintegrin-like metalloprotease domain with thrombospondin type I motifs-like 6?) 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 ADAMTSL6? plays an essential role in the development and regeneration of connective tissues. ADAMTSL6? expression rescues microfibril disorder after periodontal ligament 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 ADAMTSL6? attenuates the overactivation of TGF-? signals associated with the increased release of active TGF-? from disrupted fibrillin-1 microfibrils within periodontal ligaments. Our current data thus demonstrate the essential contribution of ADAMTSL6? to fibrillin-1 microfibril formation. These findings also suggest a new therapeutic strategy for the treatment of MFS through ADAMTSL6?-mediated fibrillin-1 microfibril assembly.

SUBMITTER: Saito M 

PROVIDER: S-EPMC3207443 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature