| First Author | Dabovic B | Year | 2015 |
| Journal | J Cell Physiol | Volume | 230 |
| Issue | 1 | Pages | 226-36 |
| PubMed ID | 24962333 | Mgi Jnum | J:279186 |
| Mgi Id | MGI:6356475 | Doi | 10.1002/jcp.24704 |
| Citation | Dabovic B, et al. (2015) Function of latent TGFbeta binding protein 4 and fibulin 5 in elastogenesis and lung development. J Cell Physiol 230(1):226-36 |
| abstractText | Mice deficient in Latent TGFbeta Binding Protein 4 (Ltbp4) display a defect in lung septation and elastogenesis. The lung septation defect is normalized by genetically decreasing TGFbeta2 levels. However, the elastic fiber assembly is not improved in Tgfb2(-/-) ;Ltbp4S(-/-) compared to Ltbp4S(-/-) lungs. We found that decreased levels of TGFbeta1 or TGFbeta3 did not improve lung septation indicating that the TGFbeta isoform elevated in Ltbp4S(-/-) lungs is TGFbeta2. Expression of a form of Ltbp4 that could not bind latent TGFbeta did not affect lung phenotype indicating that normal lung development does not require the formation of LTBP4-latent TGFbeta complexes. Therefore, the change in TGFbeta-level in the lungs is not directly related to Ltbp4 deficiency but probably is a consequence of changes in the extracellular matrix. Interestingly, combination of the Ltbp4S(-/-) mutation with a fibulin-5 null mutant in Fbln5(-/-) ;Ltbp4S(-/-) mice improves the lung septation compared to Ltbp4S(-/-) lungs. Large globular elastin aggregates characteristic for Ltbp4S(-/-) lungs do not form in Fbln5(-/-) ;Ltbp4S(-/-) lungs and EM studies showed that elastic fibers in Fbln5(-/-) ;Ltbp4S(-/-) lungs resemble those found in Fbln5(-/-) mice. These results are consistent with a role for TGFbeta2 in lung septation and for Ltbp4 in regulating fibulin-5 dependent elastic fiber assembly. |
