| First Author | Todorovic V | Year | 2011 |
| Journal | Dev Dyn | Volume | 240 |
| Issue | 1 | Pages | 176-87 |
| PubMed ID | 21181942 | Mgi Jnum | J:167709 |
| Mgi Id | MGI:4879032 | Doi | 10.1002/dvdy.22521 |
| Citation | Todorovic V, et al. (2011) Long form of latent TGF-beta binding protein 1 (Ltbp1L) regulates cardiac valve development. Dev Dyn 240(1):176-87 |
| abstractText | Transforming Growth Factor beta (TGF-beta) is crucial for valve development and homeostasis. The long form of Latent TGF-beta binding protein 1 (LTBP1L) covalently binds all TGF-beta isoforms and regulates their bioavailability. Ltbp1L expression analysis during valvulogenesis revealed two patterns of Ltbp1L production: an early one (E9.5-11.5) associated with endothelial-to-mesenchymal transformation (EMT); and a late one (E12.5 to birth) contemporaneous with valve remodeling. Similarly, histological analysis of Ltbp1L(-/-) developing valves identified two different pathologies: generation of hypoplastic endocardial cushions in early valvulogenesis, followed by development of hyperplastic valves in late valvulogenesis. Ltbp1L promotes valve EMT, as Ltbp1L absence yields hypoplastic endocardial cushions in vivo and attenuated EMT in vitro. Ltbp1L(-/-) valve hyperplasia in late valvuogenesis represents a consequence of prolonged EMT. We demonstrate that Ltbp1L is a major regulator of Tgf-beta activity during valvulogenesis since its absence results in a perturbed Tgf-beta pathway that causes all Ltbp1L(-/-) valvular defects. |
