Role of LTBP4 in alveolarization, angiogenesis, and fibrosis in lungs

Insa Bultmann-Mellin, Katharina Dinger, Carolin Debuschewitz, Katharina M.A. Loewe, Yvonne Melcher, Miro T.W. Plum, Sarah Appel, Gunter Rappl, Sebastian Willenborg, Astrid C. Schauss, Christian Jüngst, Marcus Krüger, Sven Dressler, Tomoyuki Nakamura, Frank Wempe, Miguel A.Alejandre Alcázar, Anja Sterner-Kock

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Deficiency of the extracellular matrix protein latent transforming growth factor-β (TGF-β)-binding protein-4 (LTBP4) results in lack of intact elastic fibers, which leads to disturbed pulmonary development and lack of normal alveolarization in humans and mice. Formation of alveoli and alveolar septation in pulmonary development requires the concerted interaction of extracellular matrix proteins, growth factors such as TGF-β, fibroblasts, and myofibroblasts to promote elastogenesis as well as vascular formation in the alveolar septae. To investigate the role of LTBP4 in this context, lungs of LTBP4-deficient (Ltbp4-/-) mice were analyzed in close detail. We elucidate the role of LTBP4 in pulmonary alveolarization and show that three different, interacting mechanisms might contribute to alveolar septation defects in Ltbp4-/- lungs: 1) absence of an intact elastic fiber network, 2) reduced angiogenesis, and 3) upregulation of TGF-β activity resulting in profibrotic processes in the lung.

Original languageEnglish
Pages (from-to)L687-L698
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume313
Issue number4
DOIs
StatePublished - Oct 2017
Externally publishedYes

Keywords

  • Alveolar septation
  • Angiogenesis
  • Elastic fibers
  • Latent transforming growth factor-β-binding protein-4
  • Pulmonary fibrosis

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