Open Access

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

  • Authors:
    • Lei Zhang
    • Xue Yang
    • Guoliang Jiang
    • Ying Yu
    • Jian Wu
    • Yangang Su
    • Aijun Sun
    • Yunzeng Zou
    • Hong Jiang
    • Junbo Ge
  • View Affiliations

  • Published online on: July 16, 2019     https://doi.org/10.3892/ijmm.2019.4276
  • Pages: 885-892
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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.

References

1 

Tham YK, Bernardo BC, Ooi JY, Weeks KL and McMullen JR: Pathophysiology of cardiac hypertrophy and heart failure: Signaling pathways and novel therapeutic targets. Arch Toxicol. 89:1401–1438. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Kwon HK, Jeong H, Hwang D and Park ZY: Comparative proteomic analysis of mouse models of pathological and physiological cardiac hypertrophy, with selection of biomarkers of pathological hypertrophy by integrative Proteogenomics. Biochim Biophys Acta Proteins Proteom 30118-30123. Jul 23–2018.Epub ahead of print. View Article : Google Scholar

3 

Higashikuni Y, Tanaka K, Kato M, Nureki O, Hirata Y, Nagai R, Komuro I and Sata M: Toll-like receptor-2 mediates adaptive cardiac hypertrophy in response to pressure overload through interleukin-1beta upregulation via nuclear factor kappaB activation. J Am Heart Assoc. 2:pp. e0002672013, View Article : Google Scholar

4 

Verma SK, Krishnamurthy P, Barefield D, Singh N, Gupta R, Lambers E, Thal M, Mackie A, Hoxha E, Ramirez V, et al: Interleukin-10 treatment attenuates pressure overload-induced hypertrophic remodeling and improves heart function via signal transducers and activators of transcription 3-dependent inhibition of nuclear factor-kappaB. Circulation. 126:418–429. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Sun M, Chen M, Dawood F, Zurawska U, Li JY, Parker T, Kassiri Z, Kirshenbaum LA, Arnold M, Khokha R and Liu PP: Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state. Circulation. 115:1398–1407. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Andersson U and Tracey KJ: HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 29:139–162. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L, Huang J, Yu Y, Fan XG, Yan Z, et al: HMGB1 in health and disease. Mol Aspects Med. 40:1–116. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Zhang L, Liu M, Jiang H, Yu Y, Yu P, Tong R, Wu J, Zhang S, Yao K, Zou Y and Ge J: Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure. J Cell Mol Med. 20:459–470. 2016. View Article : Google Scholar

9 

Nakamura M and Sadoshima J: Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol. 15:387–407. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Shimizu I and Minamino T: Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol. 97:245–262. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Liu R and Molkentin JD: Regulation of cardiac hypertrophy and remodeling through the dual-specificity MAPK phosphatases (DUSPs). J Mol Cell Cardiol. 101:44–49. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Ruppert C, Deiss K, Herrmann S, Vidal M, Oezkur M, Gorski A, Weidemann F, Lohse MJ and Lorenz K: Interference with ERK(Thr188) phosphorylation impairs pathological but not physiological cardiac hypertrophy. Proc Natl Acad Sci USA. 110:7440–7445. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Heineke J and Molkentin JD: Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol. 7:589–600. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Yuan L, Qiu L, Ye Y, Wu J, Wang S, Wang X, Zhou N and Zou Y: Heat-shock transcription factor 1 is critically involved in the ischaemia-induced cardiac hypertrophy via JAK2/STAT3 pathway. J Cell Mol Med. 22:4292–4303. 2018. View Article : Google Scholar : PubMed/NCBI

15 

Andrassy M, Volz HC, Igwe JC, Funke B, Eichberger SN, Kaya Z, Buss S, Autschbach F, Pleger ST, Lukic IK, et al: High-mobility group box-1 in ischemia-reperfusion injury of the heart. Circulation. 117:3216–3226. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Mir SA, Chatterjee A, Mitra A, Pathak K, Mahata SK and Sarkar S: Inhibition of signal transducer and activator of transcription 3 (STAT3) attenuates interleukin-6 (IL-6)-induced collagen synthesis and resultant hypertrophy in rat heart. J Biol Chem. 287:2666–2677. 2012. View Article : Google Scholar :

17 

Hou T, Tieu BC, Ray S, Recinos A Iii, Cui R, Tilton RG and Brasier AR: Roles of IL-6-gp130 signaling in vascular inflammation. Curr Cardiol Rev. 4:179–192. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Fritz G: RAGE: A single receptor fits multiple ligands. Trends Biochem Sci. 36:625–632. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Herzog C, Lorenz A, Gillmann HJ, Chowdhury A, Larmann J, Harendza T, Echtermeyer F, Müller M, Schmitz M, Stypmann J, et al: Thrombomodulin's lectin-like domain reduces myocardial damage by interfering with HMGB1-mediated TLR2 signalling. Cardiovasc Res. 101:400–410. 2014. View Article : Google Scholar

20 

Narayanan KB and Park HH: Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways. Apoptosis. 20:196–209. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Orliaguet G, Vivien B, Langeron O, Bouhemad B, Coriat P and Riou B: Minimum alveolar concentration of volatile anesthetics in rats during postnatal maturation. Anesthesiology. 95:734–739. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Tsukamoto A, Konishi Y, Kawakami T, Koibuchi C, Sato R, Kanai E and Inomata T: Pharmacological properties of various anesthetic protocols in 10-day-old neonatal rats. Exp Anim. 66:397–404. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Zhang L, Jiang H, Gao X, Zou Y, Liu M, Liang Y, Yu Y, Zhu W, Chen H and Ge J: Heat shock transcription factor-1 inhibits H2O2-induced apoptosis via down-regulation of reactive oxygen species in cardiac myocytes. Mol Cell Biochem. 347:21–28. 2011. View Article : Google Scholar

24 

Ehler E, Moore-Morris T and Lange S: Isolation and culture of neonatal mouse cardiomyocytes. J Vis Exp. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Zhou N, Li L, Wu J, Gong H, Niu Y, Sun A, Ge J and Zou Y: Mechanical stress-evoked but angiotensin II-independent activation of angiotensin II type 1 receptor induces cardiac hypertrophy through calcineurin pathway. Biochem Biophys Res Commun. 397:263–269. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Sadoshima J, Jahn L, Takahashi T, Kulik TJ and Izumo S: Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy J Biol Chem. 267:10551–10560. 1992.

27 

Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, et al: Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol. 6:499–506. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Kokkola R, Andersson A, Mullins G, Ostberg T, Treutiger CJ, Arnold B, Nawroth P, Andersson U, Harris RA and Harris HE: RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages. Scand J Immunol. 61:1–9. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Tzeng HP, Fan J, Vallejo JG, Dong JW, Chen X, Houser SR and Mann DL: Negative inotropic effects of high-mobility group box 1 protein in isolated contracting cardiac myocytes. Am J Physiol Heart Circ Physiol. 294:H1490–H1496. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Beetz N, Rommel C, Schnick T, Neumann E, Lother A, Monroy-Ordonez EB, Zeeb M, Preissl S, Gilsbach R, Melchior-Becker A, et al: Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload. J Mol Cell Cardiol. 101:145–155. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Su FF, Shi MQ, Guo WG, Liu XT, Wang HT, Lu ZF and Zheng QS: High-mobility group box 1 induces calcineurin-mediated cell hypertrophy in neonatal rat ventricular myocytes. Mediators Inflamm. 2012:8051492012. View Article : Google Scholar : PubMed/NCBI

32 

Zhao L, Cheng G, Jin R, Afzal MR, Samanta A, Xuan YT, Girgis M, Elias HK, Zhu Y, Davani A, et al: Deletion of Interleukin-6 Attenuates pressure overload-induced left ventricular hypertrophy and dysfunction. Circ Res. 118:1918–1929. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Shyu KG, Wang BW, Wu GJ, Lin CM and Chang H: Mechanical stretch via transforming growth factor-beta1 activates microRNA208a to regulate endoglin expression in cultured rat cardiac myoblasts. Eur J Heart Fail. 15:36–45. 2013. View Article : Google Scholar

34 

Chua S, Lee FY, Chiang HJ, Chen KH, Lu HI, Chen YT, Yang CC, Lin KC, Chen YL, Kao GS, et al: The cardioprotective effect of melatonin and exendin-4 treatment in a rat model of cardiorenal syndrome. J Pineal Res. 61:438–456. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Hou M, Gu HC, Wang HH, Liu XM, Zhou CL, Yang Q, Jiang ZR, Lin J, Wu YM, Wu YT, et al: Prenatal exposure to testosterone induces cardiac hypertrophy in adult female rats through enhanced Pkcdelta expression in cardiac myocytes. J Mol Cell Cardiol. 128:1–10. 2019. View Article : Google Scholar : PubMed/NCBI

36 

Mohan N, Kumar V, Kandala DT, Kartha CC and Laishram RS: A Splicing-independent function of RBM10 controls specific 3′ UTR processing to regulate cardiac hypertrophy. Cell Rep. 24:3539–3553. 2018. View Article : Google Scholar : PubMed/NCBI

37 

Cheng KC, Chang WT, Kuo FY, Chen ZC, Li Y and Cheng JT: TGR5 activation ameliorates hyperglycemia-induced cardiac hypertrophy in H9c2 cells. Sci Rep. 9:36332019. View Article : Google Scholar : PubMed/NCBI

38 

Schirone L, Forte M, Palmerio S, Yee D, Nocella C, Angelini F, Pagano F, Schiavon S, Bordin A, Carrizzo A, et al: A review of the molecular mechanisms underlying the development and progression of cardiac remodeling. Oxid Med Cell Longev. 2017:39201952017. View Article : Google Scholar : PubMed/NCBI

39 

Komuro I: Molecular mechanism of cardiac hypertrophy and development. Jpn Circ J. 65:353–358. 2001. View Article : Google Scholar : PubMed/NCBI

40 

Kacimi R and Gerdes AM: Alterations in G protein and MAP kinase signaling pathways during cardiac remodeling in hypertension and heart failure. Hypertension. 41:968–977. 2003. View Article : Google Scholar : PubMed/NCBI

41 

Gutkind JS and Offermanns S: A new G(q)-initiated MAPK signaling pathway in the heart. Dev Cell. 16:163–164. 2009. View Article : Google Scholar : PubMed/NCBI

42 

Reyes DRA, Gomes MJ, Rosa CM, Pagan LU, Zanati SG, Damatto RL, Rodrigues EA, Carvalho RF, Fernandes AAH, Martinez PF, et al: Exercise during transition from compensated left ventricular hypertrophy to heart failure in aortic stenosis rats. J Cell Mol Med. 23:1235–1245. 2019. View Article : Google Scholar :

43 

Kojonazarov B, Novoyatleva T, Boehm M, Happe C, Sibinska Z, Tian X, Sajjad A, Luitel H, Kriechling P, Posern G, et al: p38 MAPK inhibition improves heart function in pressure-loaded right ventricular hypertrophy. Am J Respir Cell Mol Biol. 57:603–614. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Mutlak M and Kehat I: Extracellular signal-regulated kinases 1/2 as regulators of cardiac hypertrophy. Front Pharmacol. 6:1492015. View Article : Google Scholar : PubMed/NCBI

45 

Purcell NH, Wilkins BJ, York A, Saba-El-Leil MK, Meloche S, Robbins J and Molkentin JD: Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo. Proc Natl Acad Sci USA. 104:14074–14079. 2007. View Article : Google Scholar : PubMed/NCBI

46 

Jia Z, Xue R, Liu G, Li L, Yang J, Pi G, Ma S and Kan Q: HMGB1 is involved in the protective effect of the PPARα agonist fenofibrate against cardiac hypertrophy. PPAR Res. 2014:5413942014. View Article : Google Scholar

47 

Funayama A, Shishido T, Netsu S, Narumi T, Kadowaki S, Takahashi H, Miyamoto T, Watanabe T, Woo CH, Abe J, et al: Cardiac nuclear high mobility group box 1 prevents the development of cardiac hypertrophy and heart failure. Cardiovasc Res. 99:657–664. 2013. View Article : Google Scholar : PubMed/NCBI

48 

Sessa L, Gatti E, Zeni F, Antonelli A, Catucci A, Koch M, Pompilio G, Fritz G, Raucci A and Bianchi ME: The receptor for advanced glycation end-products (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs). PLoS One. 9:pp. e869032014, View Article : Google Scholar : PubMed/NCBI

49 

Nonaka K, Kajiura Y, Bando M, Sakamoto E, Inagaki Y, Lew JH, Naruishi K, Ikuta T, Yoshida K, Kobayashi T, et al: Advanced glycation end-products increase IL-6 and ICAM-1 expression via RAGE, MAPK and NF-kappaB pathways in human gingival fibroblasts. J Periodontal Res. 53:334–344. 2018. View Article : Google Scholar

50 

Wu CZ, Zheng JJ, Bai YH, Xia P, Zhang HC and Guo Y: HMGB1/RAGE axis mediates the apoptosis, invasion, autophagy, and angiogenesis of the renal cell carcinoma. Onco Targets Ther. 11:4501–4510. 2018. View Article : Google Scholar : PubMed/NCBI

51 

Kim J, Park JC, Lee MH, Yang CE, Lee JH and Lee WJ: High-mobility group Box 1 mediates fibroblast activity via RAGE-MAPK and NF-kappaB signaling in keloid scar formation. Int J Mol Sci. 19:E762017. View Article : Google Scholar

52 

Ha T, Li Y, Hua F, Ma J, Gao X, Kelley J, Zhao A, Haddad GE, Williams DL, William Browder I, et al: Reduced cardiac hypertrophy in toll-like receptor 4-deficient mice following pressure overload. Cardiovasc Res. 68:224–234. 2005. View Article : Google Scholar : PubMed/NCBI

53 

Ehrentraut H, Weber C, Ehrentraut S, Schwederski M, Boehm O, Knuefermann P, Meyer R and Baumgarten G: The toll-like receptor 4-antagonist eritoran reduces murine cardiac hypertrophy. Eur J Heart Fail. 13:602–610. 2011. View Article : Google Scholar : PubMed/NCBI

54 

Jiang DS, Zhang XF, Gao L, Zong J, Zhou H, Liu Y, Zhang Y, Bian ZY, Zhu LH, Fan GC, et al: Signal regulatory protein-alpha protects against cardiac hypertrophy via the disruption of toll-like receptor 4 signaling. Hypertension. 63:96–104. 2014. View Article : Google Scholar

Related Articles

Journal Cover

September 2019
Volume 44 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Zhang, L., Yang, X., Jiang, G., Yu, Y., Wu, J., Su, Y. ... Ge, J. (2019). HMGB1 enhances mechanical stress-induced cardiomyocyte hypertrophy in vitro via the RAGE/ERK1/2 signaling pathway. International Journal of Molecular Medicine, 44, 885-892. https://doi.org/10.3892/ijmm.2019.4276
MLA
Zhang, L., Yang, X., Jiang, G., Yu, Y., Wu, J., Su, Y., Sun, A., Zou, Y., Jiang, H., Ge, J."HMGB1 enhances mechanical stress-induced cardiomyocyte hypertrophy in vitro via the RAGE/ERK1/2 signaling pathway". International Journal of Molecular Medicine 44.3 (2019): 885-892.
Chicago
Zhang, L., Yang, X., Jiang, G., Yu, Y., Wu, J., Su, Y., Sun, A., Zou, Y., Jiang, H., Ge, J."HMGB1 enhances mechanical stress-induced cardiomyocyte hypertrophy in vitro via the RAGE/ERK1/2 signaling pathway". International Journal of Molecular Medicine 44, no. 3 (2019): 885-892. https://doi.org/10.3892/ijmm.2019.4276