論文 - 詳細
| RRC ID | 69624 |
|---|---|
| 著者 | Saito M, Kurokawa M, Oda M, Oshima M, Tsutsui K, Kosaka K, Nakao K, Ogawa M, Manabe RI, Suda N, Ganjargal G, Hada Y, Noguchi T, Teranaka T, Sekiguchi K, Yoneda T, Tsuji T. |
| タイトル | ADAMTSL6β protein rescues fibrillin-1 microfibril disorder in a Marfan syndrome mouse model through the promotion of fibrillin-1 assembly. |
| ジャーナル | J Biol Chem |
| 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. ADAMTSL6β (A disintegrin-like metalloprotease domain with thrombospondin type I motifs-like 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 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 overactivation of TGF-β signals associated with the increased release of active TGF-β from disrupted fibrillin-1 microfibrils within periodontal ligaments. 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. |
| 巻・号 | 286(44) |
| ページ | 38602-38613 |
| 公開日 | 2011-11-4 |
| DOI | 10.1074/jbc.M111.243451 |
| PII | S0021-9258(20)50703-5 |
| PMID | 21880733 |
| PMC | PMC3207443 |
| MeSH | Animals Disease Models, Animal Extracellular Matrix / metabolism Extracellular Matrix Proteins / genetics* Extracellular Matrix Proteins / physiology Fibrillin-1 Fibrillins Gene Expression Regulation, Developmental Humans Immunohistochemistry / methods Marfan Syndrome / metabolism* Mice Mice, Inbred C57BL Mice, Transgenic Microfibrils / pathology Microfilament Proteins / chemistry* Models, Genetic Recombinant Proteins / chemistry Tooth / embryology Transforming Growth Factor beta / metabolism Wound Healing |
| IF | 4.238 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |