HMGB1 enhances mechanical stress-induced cardiomyocyte hypertrophy in�vitro via the RAGE/ERK1/2 signaling pathway

Pressure overload‑induced cardiac hypertrophy is associated with a complex spectrum of pathophysiological mechanisms, including the inflammation response. High mobility group box‑1 (HMGB1), a pro‑inflammatory cytokine, is not only increased in myocardium under pressure overload, but also exacerbates pressure overload‑induced cardiac hypertrophy and dysfunction; however, the underlying mechanisms have remained elusive. In the present study, cultured cardiomyocytes were stimulated by mechanical stress and/or HMGB1 for various durations to examine the role of HMGB1 in cardiomyocyte hypertrophy, and to detect the expression of receptor for advanced glycation end products (RAGE), toll‑like receptor 4 (TLR‑4) and the activation status of mitogen‑activated protein kinases (MAPKs) and Janus kinase 2 (JAK2)/STAT3. The results indicated that HMGB1 aggravated mechanical stress‑induced cardiomyocyte hypertrophy. Furthermore, mechanical stress and HMGB1 stimulation activated extracellular signal‑regulated kinase 1/2 (ERK1/2), P38 and JAK2/STAT3 signaling in cardiomyocytes, but an additive effect of the combined stimuli was only observed on the activation of ERK1/2. In addition, mechanical stress caused a prompt upregulation of the expression of RAGE and TLR‑4 in cardiomyocytes, while the activation of ERK1/2 by HMGB1 was inhibited by blockage of RAGE, but not by blockage of TLR‑4. In summary, the present results indicated that extracellular HMGB1 enhanced mechanical stress‑induced cardiomyocyte hypertrophy in vitro, at least partially via the RAGE/ERK1/2 signaling pathway.