Background We have previously identified and characterised a novel gene, designated myocyte stress 1 (ms1), which is upregulated within 1 h in the left ventricle following aortic banding in the rat, suggesting a possible role for ms1 in the initial signalling of the hypertrophic response. ms1 is also expressed during cardiac development and is transiently upregulated during ischaemia–reperfusion in vitro. This suggests that ms1 may play a more widespread role in cardiac physiology. This is further supported by findings showing that ms1 can stimulate serum response factor (SRF)-dependent transcription by inducing the nuclear accumulation of myocardin-related transcription factors (MRTF) A and B through a mechanism dependent on RhoA and actin polymerisation. The aim of this study was to determine whether ms1 induces cardiac cell hypertrophy directly and protects such cells against apoptosis.
Methods ms1 was transiently overexpressed in a heart-derived rat cell line, H9c2, by plasmid transfection. Empty vector transfection was used as a control. We examined the effect of ms1 overexpression on cell size, proliferation and ability to protect against staurosporine-induced apoptotic cell death. In addition, to identify putative target genes and downstream pathways to ms1, altered gene expression following ms1 overexpression was examined.
Results Transient overexpression of ms1 in H9c2 altered the expression of known hypertrophic and cardioprotective target genes of the MRTF/SRF transcriptional pathway (cardiac α-actin, brain natriuretic peptide, IL-6, leukemia inhibitory factor, apoptosis repressor with caspase recruitment domain and adrenomedullin). The size of cells overexpressing ms1 was significantly increased by an average of 47% when compared with empty vector control (p<0.01) and overexpression of ms1 markedly inhibited staurosporine-induced apoptosis by approximately 89%, p<0.01 (ms1 transfected cells, 3.5% ± 1.0% vs empty vector control, 32.4% ± 3.8%).
Conclusions These findings suggest that ms1 induces a hypertrophic response and provides cardioprotection possibly via a MRTF–SRF signalling mechanism. The findings for the first time provide direct evidence of the involvement of ms1 in hypertrophy and cardioprotection.