DsiRNA Knockdowns of the Hippo Pathway Regulators Promote Cardiac Myocyte Replication

Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

In the event of a heart attack, many cardiac myocytes are irreversibly lost and cannot be replaced, which can lead to heart failure. Several investigations have proved that the Hippo pathway can be manipulated to benefit cardiac myocyte recovery. The Hippo pathway is a cell-signaling pathway involved in cellular proliferation, stem cell differentiation, control of organ size and apoptosis. The pathway’s main effector is a transcriptional co-factor YAP (Yes-associated protein) whose activation is controlled by different regulators like SAV1 (Salvador Homolog 1), NF2 (Neurofibromin 2) and MOB1 (Mps one binder kinase activator). We investigated using DsiRNAs to manipulate the expression of these regulators in cultured cardiac myocytes for their potential in heart tissue healing and protection.Highly potent Dicer substrate siRNAs (DsiRNAs) were used to silence upstream core regulators of the pathway: MOB1, NF2 and SAV1. The DsiRNAs successfully lowered the level of the corresponding genes and proteins. A combination of NF2 and SAV1 knockdowns is more potent than individual knockdowns. However, MOB1 silencing alone, is a very promising target for heart regeneration, was more efficacious than silencing by either NF2 and or SAV1 individually.

Article activity feed