Roles of fibronectin isoforms in neonatal vascular development and matrix integrity

Kumra, Heena, Sabatier, Laetitia, Hassan, Amani, Sakai, Takao ORCID: 0000-0002-7375-5450, Mosher, Deane, Brinckmann, Jurgen and Reinhardt, Dieter (2018) Roles of fibronectin isoforms in neonatal vascular development and matrix integrity. PLoS Biology, 16 (7). e2004812-.

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Abstract

Fibronectin (FN) exists in two forms—plasma FN (pFN) and cellular FN (cFN). Although the role of FN in embryonic blood vessel development is well established, its function and the contribution of individual isoforms in early postnatal vascular development are poorly understood. Here, we employed a tamoxifen-dependent cFN inducible knockout (cFN iKO) mouse model to study the consequences of postnatal cFN deletion in smooth muscle cells (SMCs), the major cell type in the vascular wall. Deletion of cFN influences collagen deposition but does not affect life span. Unexpectedly, pFN translocated to the aortic wall in the cFN iKO and in control mice, possibly rescuing the loss of cFN. Postnatal pFN deletion did not show a histological aortic phenotype. Double knockout (dKO) mice lacking both, cFN in SMCs and pFN, resulted in postnatal lethality. These data demonstrate a safeguard role of pFN in vascular stability and the dispensability of the individual FN isoforms in postnatal vascular development. Complete absence of FNs in the dKOs resulted in a disorganized tunica media of the aortic wall. Matrix analysis revealed common and differential roles of the FN isoforms in guiding the assembly/deposition of elastogenic extracellular matrix (ECM) proteins in the aortic wall. In addition, we determined with two cell culture models that that the two FN isoforms acted similarly in supporting matrix formation with a greater contribution from cFN. Together, these data show that pFN exerts a critical role in safeguarding vascular organization and health, and that the two FN isoforms function in an overlapping as well as distinct manner to maintain postnatal vascular matrix integrity.

Item Type:	Article
Uncontrolled Keywords:	Muscle, Smooth, Aorta, Elastic Tissue, Extracellular Matrix, Animals, Animals, Newborn, Mice, Knockout, Fibronectins, Protein Isoforms, Survival Analysis, Organ Specificity, Gene Deletion, Genotype, Phenotype
Depositing User:	Symplectic Admin
Date Deposited:	25 Jul 2018 08:06
Last Modified:	19 Jan 2023 01:30
DOI:	10.1371/journal.pbio.2004812
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3024151