Targeting Transforming Growth Factor Beta Receptors in Pulmonary Hypertension
Résumé
The transforming growth factor (TGF)-β superfamily includes several groups of multifunctional
proteins that form two major branches, namely the TGF-β/activin/nodal branch and the bone
morphogenetic protein (BMP)/growth differentiation factor (GDF) branch. The response to the
activation of these two branches, acting through canonical (Smad 2/3 and Smad 1/5/8, respectively)
and noncanonical signaling pathways, are diverse and vary amongst different environmental
conditions and cell types. An extensive body of data gathered in recent years has demonstrated a central
role for the cross-talk between these two branches in a number of cellular processes that include the
regulation of cell proliferation and differentiation, as well as the transduction of signaling cascades for
the development and maintenance of different tissues and organs. Importantly, alterations in these
pathways that include heterozygous germline mutations and/or alterations in the expression of several
constitutive members have been identified in patients with familial/heritable or idiopathic pulmonary
arterial hypertension (PAH). Consequently, loss or dysfunctions in the delicate, finely tuned balance
between the TGF-β/activin/nodal branch and the BMP/GDF branch are currently viewed as the major
molecular defect playing a critical role in PAH predisposition and disease progression. Here we review
the role of the TGF-β/activin/nodal branch in PAH and illustrate how this knowledge has not only
provided insight to understand its pathogenesis, but also paved the way for possible novel therapeutic
approaches.
Origine : Fichiers produits par l'(les) auteur(s)
Loading...