| First Author | Schissel SL | Year | 2009 |
| Journal | Am J Pathol | Volume | 174 |
| Issue | 3 | Pages | 818-28 |
| PubMed ID | 19179605 | Mgi Jnum | J:146283 |
| Mgi Id | MGI:3837229 | Doi | 10.2353/ajpath.2009.080856 |
| Citation | Schissel SL, et al. (2009) Aortic carboxypeptidase-like protein is expressed in fibrotic human lung and its absence protects against bleomycin-induced lung fibrosis. Am J Pathol 174(3):818-28 |
| abstractText | The pathological hallmarks of idiopathic pulmonary fibrosis include proliferating fibroblasts and myofibroblasts, as well as excessive collagen matrix deposition. In addition, both myofibroblast contraction and remodeling of the collagen-rich matrix contribute to the abnormal structure and function of the fibrotic lung. Little is known, however, about collagen-associated proteins that promote fibroblast and myofibroblast retention, as well as the proliferation of these cells on the extracellular matrix. In this study, we demonstrate that aortic carboxypeptidase-like protein (ACLP), a collagen-associated protein with a discoidin-like domain, is expressed at high levels in human fibrotic lung tissue and human fibroblasts, and that its expression increases markedly in the lungs of bleomycin-injured mice. Importantly, ACLP-deficient mice accumulated significantly fewer myofibroblasts and less collagen in the lung after bleomycin injury, as compared with wild-type controls, despite equivalent levels of bleomycin-induced inflammation. ACLP that is secreted by lung fibroblasts was retained on fibrillar collagen, and ACLP-deficient lung fibroblasts that were cultured on collagen exhibited changes in cell spreading, proliferation, and contraction of the collagen matrix. Finally, the addition of recombinant discoidin-like domain of ACLP to cultured ACLP-deficient lung fibroblasts restored cell spreading and increased the contraction of collagen gels. Therefore, both ACLP and its discoidin-like domain may be novel targets for anti-myofibroblast-based therapies for the treatment of pulmonary fibrosis. |
