MicroRNA-138 plays a role in hypoxic pulmonary vascular remodelling by targeting Mst1

Unbalanced apoptosis is a major cause of structural remodeling of vasculatures associated with pulmonary arterial hypertension (PAH), while the underlying mechanisms are still elusive. MicroRNAs (miRNAs) regulate the expression of several proteins that are important for the cell fate including differentiation, proliferation and apoptosis. It is possible that these regulatory RNA molecules play a role in the development of PAH. To test this hypothesis, we studied the effect of several miRNAs on the apoptosis of cultured pulmonary artery smooth muscle cells (PASMCs), and identified miR-138 to be an important player. The miR-138 was expressed in PASMCs, and its expression is subject to hypoxia regulation. Expression of exogenous miR-138 suppressed PASMC apoptosis, prevented caspase activation, and disrupted the Bcl-2 signaling. The serine-threonine kinase (Mst1), an amplifier of cell apoptosis, seemed to be a target of miR-138, and the activation of the Akt pathway was necessary for the antiapoptotic effect of miR-138. Therefore, these results suggest that miR-138 appears to be a negative regulator of PASMC apoptosis, and play an important role in HPVR.

Source: BJ Cell - March 13, 2013 Category: Biochemistry Authors: S Li, Y Ran, D Zhang, J Chen, S Li, D Zhu Tags: BJ Cell Source Type: research