Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8.

ABSTRACT:

Rationale

Heritable pulmonary arterial hypertension (HPAH) is primarily caused by mutations of the bone morphogenetic protein (BMP) type-II receptor (BMPR2). Recent identification of mutations in the downstream mediator Smad-8 (gene, SMAD9) was surprising, because loss of Smad-8 function in canonical BMP signaling is largely compensated by Smad-1 and -5. We therefore hypothesized that noncanonical pathways may play an important role in PAH.

Objectives

To determine whether HPAH mutations disrupt noncanonical Smad-mediated microRNA (miR) processing.

Methods

Expression of miR-21, miR-27a, and miR-100 was studied in pulmonary artery endothelial (PAEC) and pulmonary artery smooth muscle cells (PASMC) from explant lungs of patients with PAH.

Measurements and main results

SUBMITTER: Drake KM 

PROVIDER: S-EPMC3262031 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature