Inhibition of histone demethylase JMJD1C attenuates cardiac hypertrophy and fibrosis induced by angiotensin II

. Immunofluorescence staining showed that the treatment of Ang II could increase cardiomyocyte size. RT-qPCR results have shown that Ang II could increase the expression of cell hypertrophic and fibrotic markers in H9c2 cells. Whereas, inhibition of JMJD1C by shRNA and JIB-04, a small molecule histone demethylase inhibitor, significantly reduced Ang II-induced cell hypertrophy, and hypertrophic and fibrotic marker overexpression. Furthermore, cardiomyocyte JMJD1C knockdown decreased Tissue Inhibitor of Metalloproteinases 1 (TIMP1) transcription with pro-fibrotic activity. In conclusion, JMJD1C plays an important role in Ang II-induced cardiac hypertrophy and fibrosis by activating TIMP1 transcription, targeting of JMJD1C may be an effective strategy for the treatment of Ang II-associated cardiac diseases.