Lysine demethylase 3A is a positive regulator of cardiac myofibroblast transdifferentiation that increases Smad3 phosphorylation following transforming growth factor beta1 stimulation.

Abstract

The epigenetic modifier molecule lysine demethylase 3A (KDM3A) has been shown to help ameliorate cardiovascular diseases, but its effect on cardiac fibroblasts (CFs) remains unclear. We designed gain- and loss-of-function experiments to investigate the biological functions of KDM3A in CFs. Moreover, we used SIS3-HCl (a specific inhibitor of p-Smad3) to explore the underlying mechanism. Cell viability and migration were verified by CCK-8 and cell migration experiments, respectively, and the degree of fibrosis was measured by Western blot analysis. Our data revealed that KDM3A enhanced the proliferation and migration of CFs and increased the fibroblast-to-myofibroblast transition while enabling the Smad3 phosphorylation response to transforming growth factor beta1 (TGFβ1) stimulation. However, these effects were abolished by SIS3-HCl. Furthermore, KDM3A inhibition obviously protected against cardiac myofibroblast transdifferentiation under TGFβ1 stimulation. KDM3A may act as a novel regulator of cardiac myofibroblast transdifferentiation through its ability to modulate the phosphorylation of Smad3 following TGFβ1 stimulation.