Specificity of latent TGF-β binding protein (LTBP) incorporation into matrix: Role of fibrillins and fibronectin

Lior Zilberberg, Vesna Todorovic, Branka Dabovic, Masahito Horiguchi, Thomas Couroussé, Lynn Sakai, Daniel B. Rifkin

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Fibrillin microfibrils are extracellular matrix structures with essential functions in the development and the organization of tissues including blood vessels, bone, limbs and the eye. Fibrillin-1 and fibrillin-2 form the core of fibrillin microfibrils, to which multiple proteins associate to form a highly organized structure. Defining the components of this structure and their interactions is crucial to understand the pathobiology of microfibrillopathies associated with mutations in fibrillins and in microfibril-associated molecules. In this study, we have analyzed both in vitro and in vivo the role of fibrillin microfibrils in the matrix deposition of latent TGF-β binding protein 1 (LTBP-1), -3 and -4; the three LTBPs that form a complex with TGF-β. In Fbn1 -/- ascending aortas and lungs, LTBP-3 and LTBP-4 are not incorporated into a matrix lacking fibrillin-1 microfibrils, whereas LTBP-1 is still deposited. In addition, in cultures of Fbn1 -/- smooth muscle cells or lung fibroblasts, LTBP-3 and LTBP-4 are not incorporated into a matrix lacking fibrillin-1 microfibrils, whereas LTBP-1 is still deposited. Fibrillin-2 is not involved in the deposition of LTBP-1 in Fbn1 -/- extracellular matrix as cells deficient for both fibrillin-1 and fibrillin-2 still incorporate LTBP-1 in their matrix. However, blocking the formation of the fibronectin network in Fbn1 -/- cells abrogates the deposition of LTBP-1. Together, these data indicate that LTBP-3 and LTBP-4 association with the matrix depends on fibrillin-1 microfibrils, whereas LTBP-1 association depends on a fibronectin network.

Original languageEnglish (US)
Pages (from-to)3828-3836
Number of pages9
JournalJournal of Cellular Physiology
Volume227
Issue number12
DOIs
StatePublished - Dec 1 2012

Fingerprint

Fibronectins
Carrier Proteins
Microfibrils
Fibrillins
Extracellular Matrix
Lung
Blood vessels
Fibroblasts
Cell culture
Smooth Muscle Myocytes
Blood Vessels
Muscle
Aorta
Bone
Extremities
Cells
Fibrillin-1
Tissue
Bone and Bones

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Specificity of latent TGF-β binding protein (LTBP) incorporation into matrix : Role of fibrillins and fibronectin. / Zilberberg, Lior; Todorovic, Vesna; Dabovic, Branka; Horiguchi, Masahito; Couroussé, Thomas; Sakai, Lynn; Rifkin, Daniel B.

In: Journal of Cellular Physiology, Vol. 227, No. 12, 01.12.2012, p. 3828-3836.

Research output: Contribution to journalArticle

Zilberberg, L, Todorovic, V, Dabovic, B, Horiguchi, M, Couroussé, T, Sakai, L & Rifkin, DB 2012, 'Specificity of latent TGF-β binding protein (LTBP) incorporation into matrix: Role of fibrillins and fibronectin', Journal of Cellular Physiology, vol. 227, no. 12, pp. 3828-3836. https://doi.org/10.1002/jcp.24094
Zilberberg, Lior ; Todorovic, Vesna ; Dabovic, Branka ; Horiguchi, Masahito ; Couroussé, Thomas ; Sakai, Lynn ; Rifkin, Daniel B. / Specificity of latent TGF-β binding protein (LTBP) incorporation into matrix : Role of fibrillins and fibronectin. In: Journal of Cellular Physiology. 2012 ; Vol. 227, No. 12. pp. 3828-3836.
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AU - Couroussé, Thomas

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AU - Rifkin, Daniel B.

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AB - Fibrillin microfibrils are extracellular matrix structures with essential functions in the development and the organization of tissues including blood vessels, bone, limbs and the eye. Fibrillin-1 and fibrillin-2 form the core of fibrillin microfibrils, to which multiple proteins associate to form a highly organized structure. Defining the components of this structure and their interactions is crucial to understand the pathobiology of microfibrillopathies associated with mutations in fibrillins and in microfibril-associated molecules. In this study, we have analyzed both in vitro and in vivo the role of fibrillin microfibrils in the matrix deposition of latent TGF-β binding protein 1 (LTBP-1), -3 and -4; the three LTBPs that form a complex with TGF-β. In Fbn1 -/- ascending aortas and lungs, LTBP-3 and LTBP-4 are not incorporated into a matrix lacking fibrillin-1 microfibrils, whereas LTBP-1 is still deposited. In addition, in cultures of Fbn1 -/- smooth muscle cells or lung fibroblasts, LTBP-3 and LTBP-4 are not incorporated into a matrix lacking fibrillin-1 microfibrils, whereas LTBP-1 is still deposited. Fibrillin-2 is not involved in the deposition of LTBP-1 in Fbn1 -/- extracellular matrix as cells deficient for both fibrillin-1 and fibrillin-2 still incorporate LTBP-1 in their matrix. However, blocking the formation of the fibronectin network in Fbn1 -/- cells abrogates the deposition of LTBP-1. Together, these data indicate that LTBP-3 and LTBP-4 association with the matrix depends on fibrillin-1 microfibrils, whereas LTBP-1 association depends on a fibronectin network.

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