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© Research
Publication : Developmental dynamics : an official publication of the American Association of Anatomists

Long form of latent TGF-β binding protein 1 (Ltbp1L) regulates cardiac valve development

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Developmental dynamics : an official publication of the American Association of Anatomists - 01 Jan 2011

Todorovic V, Finnegan E, Freyer L, Zilberberg L, Ota M, Rifkin DB

Link to Pubmed [PMID] – 21181942

Dev. Dyn. 2011 Jan;240(1):176-87

Transforming Growth Factor β (TGF-β) is crucial for valve development and homeostasis. The long form of Latent TGF-β binding protein 1 (LTBP1L) covalently binds all TGF-β isoforms and regulates their bioavailability. Ltbp1L expression analysis during valvulogenesis revealed two patterns of Ltbp1L production: an early one (E9.5-11.5) associated with endothelial-to-mesenchymal transformation (EMT); and a late one (E12.5 to birth) contemporaneous with valve remodeling. Similarly, histological analysis of Ltbp1L(-/-) developing valves identified two different pathologies: generation of hypoplastic endocardial cushions in early valvulogenesis, followed by development of hyperplastic valves in late valvulogenesis. Ltbp1L promotes valve EMT, as Ltbp1L absence yields hypoplastic endocardial cushions in vivo and attenuated EMT in vitro. Ltbp1L(-/-) valve hyperplasia in late valvuogenesis represents a consequence of prolonged EMT. We demonstrate that Ltbp1L is a major regulator of Tgf-β activity during valvulogenesis since its absence results in a perturbed Tgf-β pathway that causes all Ltbp1L(-/-) valvular defects.

https://www.ncbi.nlm.nih.gov/pubmed/21181942