Control of lung development by latent TGF-β binding proteins

Branka Dabovic, Yan Chen, Jiwon Choi, Elaine C. Davis, Lynn Sakai, Vesna Todorovic, Melinda Vassallo, Lior Zilberberg, Amanjot Singh, Daniel B. Rifkin

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The latent TGF-β binding proteins (LTBP-1 -3, and -4) assist in the secretion and localization of latent TGF-β molecules. Ltbp3-/-and Ltbp4S-/- mice have distinct phenotypes and only in the lungs does deficiency of either Ltbp-3 or Ltbp-4 cause developmental abnormalities. To determine if these two LTBPs have additional common functions, we generated mice deficient for both Ltbp-3 and Ltbp-4S. The only novel defect in Ltbp3-/-;Ltbp4S-/- mice was an early lethality compared to mice with single mutations. In addition lung abnormalities were exacerbated and the terminal air sac septation defect was more severe in Ltbp3-/-;Ltbp4S-/- mice than in Ltbp4S-/- mice. Decreased cellularity of Ltbp3-/-;Ltbp4S-/- lungs was correlated with higher rate of apoptosis in newborn lungs of Ltbp3-/-;Ltbp4S-/- animals compared to WT, Ltbp3-/-, and Ltbp4S-/- mice. No differences in the maturation of the major lung cell types were discerned between the single and double mutant mice. However, the distribution of type 2 cells and myofibroblasts was abnormal, and myofibroblast segregation in some areas might be an indication of early fibrosis. We also observed differences in ECM composition between Ltbp3-/-;Ltbp4S-/- and Ltbp4S-/- lungs after birth, reflected in decreased incorporation of fibrillin-1 and -2 in Ltbp3-/-;Ltbp4S-/- matrix. The function of the lungs of Ltbp3-/-;Ltbp4S-/- mice after the first week of life was potentially further compromised by macrophage infiltration, as proteases secreted from macrophages might exacerbate developmental emphysema. Together these data indicate that LTBP-3 and -4 perform partially overlapping functions only in the lungs.

Original languageEnglish (US)
Pages (from-to)1499-1509
Number of pages11
JournalJournal of Cellular Physiology
Volume226
Issue number6
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

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Carrier Proteins
Macrophages
Lung
Military electronic countermeasures
Defects
Airports
Infiltration
Animals
Peptide Hydrolases
Myofibroblasts
Apoptosis
Molecules
Chemical analysis
Air Sacs
Emphysema
Fibrosis
Parturition
Phenotype
Mutation

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Dabovic, B., Chen, Y., Choi, J., Davis, E. C., Sakai, L., Todorovic, V., ... Rifkin, D. B. (2011). Control of lung development by latent TGF-β binding proteins. Journal of Cellular Physiology, 226(6), 1499-1509. https://doi.org/10.1002/jcp.22479

Control of lung development by latent TGF-β binding proteins. / Dabovic, Branka; Chen, Yan; Choi, Jiwon; Davis, Elaine C.; Sakai, Lynn; Todorovic, Vesna; Vassallo, Melinda; Zilberberg, Lior; Singh, Amanjot; Rifkin, Daniel B.

In: Journal of Cellular Physiology, Vol. 226, No. 6, 01.06.2011, p. 1499-1509.

Research output: Contribution to journalArticle

Dabovic, B, Chen, Y, Choi, J, Davis, EC, Sakai, L, Todorovic, V, Vassallo, M, Zilberberg, L, Singh, A & Rifkin, DB 2011, 'Control of lung development by latent TGF-β binding proteins', Journal of Cellular Physiology, vol. 226, no. 6, pp. 1499-1509. https://doi.org/10.1002/jcp.22479
Dabovic B, Chen Y, Choi J, Davis EC, Sakai L, Todorovic V et al. Control of lung development by latent TGF-β binding proteins. Journal of Cellular Physiology. 2011 Jun 1;226(6):1499-1509. https://doi.org/10.1002/jcp.22479
Dabovic, Branka ; Chen, Yan ; Choi, Jiwon ; Davis, Elaine C. ; Sakai, Lynn ; Todorovic, Vesna ; Vassallo, Melinda ; Zilberberg, Lior ; Singh, Amanjot ; Rifkin, Daniel B. / Control of lung development by latent TGF-β binding proteins. In: Journal of Cellular Physiology. 2011 ; Vol. 226, No. 6. pp. 1499-1509.
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