Volume 22, Issue 4 (2019)
mjms 2019, 22(4): 173-180 |
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Borjian Fard M, Choobineh S, Soori R, Mazaheri Z. Investigating role of the JAK/STAT pathway in cardiac hypertrophy induced by the interval and continuous trainings in adult male rats. mjms 2019; 22 (4) :173-180
URL: http://mjms.modares.ac.ir/article-30-24491-en.html
URL: http://mjms.modares.ac.ir/article-30-24491-en.html
1- Exercise Physiology Department, Physical Education Faculty, University of Tehran, Tehran, Iran
2- Exercise Physiology Department, Physical Education Faculty, University of Tehran, Tehran, Iran ,choobineh@ut.ac.ir
3- Basic Medical Science Research Center, Pasargad Tissue & Gene Technology Company, Tehran, Iran
2- Exercise Physiology Department, Physical Education Faculty, University of Tehran, Tehran, Iran ,
3- Basic Medical Science Research Center, Pasargad Tissue & Gene Technology Company, Tehran, Iran
Abstract: (7154 Views)
Aims: The JAK/STAT signaling pathway is activated by an interlacing-6 family of proteins and plays a crucial role in the hypertrophy process. Also, examining the role of this pathway in cardiac physiological hypertrophy derived by endurance training was the ultimate aim of this research.
Material & Methods: 16 adult male Wistar rats (age, weeks) were used in this research. The rats were selected at random and assigned to one of two groups: Control and endurance training groups (8 rats in each group). Endurance training groups’ rats trained 8 weeks, 5 days/week. 48 hours after the last session, the rats were euthanized. The cardiac tissue was separated and cardiac hypertrophy was measured through considering heart weight to body weight ratio, left ventricle wall thickness, and cardiomyocytes area. In addition, expression levels of CT1, gp130, JAK2, and STAT3 genes were measured by real-time PCR. Finally, the data were analyzed by the independent t-test. Differences were considered significant at p<0.05.
Findings: The endurance training group had a significant increase in the heart weight to body weight ratio compared with the control group (p≤0.0001). Moreover, analyses performed by staining with Hematoxylin Eosin, shown that the training group had significant increases in the thickness of the left ventricle (p≤0.0001). Yet, measuring expression levels of studied genes revealed that there were no significant differences between the training group and the control group expression levels (CT1: P=0.174, gp130: P=0.054, JAK2: P=0.423, STAT3: P=0.062).
Conclusion: Expression profiling in the training group performed after 8 weeks of training, revealed that the expression levels of genes involved in JAK/STAT pathway genes were not changed significantly. These findings suggest that despite the protective role, the JAK/STAT pathway may not play a crucial role in physiological cardiac hypertrophy.
Material & Methods: 16 adult male Wistar rats (age, weeks) were used in this research. The rats were selected at random and assigned to one of two groups: Control and endurance training groups (8 rats in each group). Endurance training groups’ rats trained 8 weeks, 5 days/week. 48 hours after the last session, the rats were euthanized. The cardiac tissue was separated and cardiac hypertrophy was measured through considering heart weight to body weight ratio, left ventricle wall thickness, and cardiomyocytes area. In addition, expression levels of CT1, gp130, JAK2, and STAT3 genes were measured by real-time PCR. Finally, the data were analyzed by the independent t-test. Differences were considered significant at p<0.05.
Findings: The endurance training group had a significant increase in the heart weight to body weight ratio compared with the control group (p≤0.0001). Moreover, analyses performed by staining with Hematoxylin Eosin, shown that the training group had significant increases in the thickness of the left ventricle (p≤0.0001). Yet, measuring expression levels of studied genes revealed that there were no significant differences between the training group and the control group expression levels (CT1: P=0.174, gp130: P=0.054, JAK2: P=0.423, STAT3: P=0.062).
Conclusion: Expression profiling in the training group performed after 8 weeks of training, revealed that the expression levels of genes involved in JAK/STAT pathway genes were not changed significantly. These findings suggest that despite the protective role, the JAK/STAT pathway may not play a crucial role in physiological cardiac hypertrophy.
Keywords: cardiac hypertrophy
exercise
adult rat
Article Type: Original Research |
Subject:
Sport physiology
Received: 2018/09/16 | Accepted: 2019/09/15
Received: 2018/09/16 | Accepted: 2019/09/15
References
1. Abdul-Ghani M, Suen C, Jiang B, Deng Y, Weldrick JJ, Putinski Ch, et al. Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart. Cell Res. 2017;27(10):1195-215. [Link] [DOI:10.1038/cr.2017.87]
2. Xiao J, Xu T, Li J, Lv D, Chen P, Zhou Q, et al. Exercise-induced physiological hypertrophy initiates activation of cardiac progenitor cells. Int J Clin Exp Pathol. 2014;7(2):663-9. [Link]
3. Bernardo BC, Weeks KL, Pretorius L, McMullen JR. Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies. Pharmacol Ther. 2010;128(1):191-227. [Link] [DOI:10.1016/j.pharmthera.2010.04.005]
4. Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol. 2018;15(7):387-407. [Link] [DOI:10.1038/s41569-018-0007-y]
5. Xiao J, Chen P, Qu Y, Yu P, Yao J, Wang H, et al. Telocytes in exercise‐induced cardiac growth. J Cell Mol Med. 2016;20(5):973-9. [Link] [DOI:10.1111/jcmm.12815]
6. Tham YK, Bernardo BC, Ooi JY, Weeks KL, McMullen JR. Pathophysiology of cardiac hypertrophy and heart failure: Signaling pathways and novel therapeutic targets. Arch Toxicol. 2015;89(9):1401-38. [Link] [DOI:10.1007/s00204-015-1477-x]
7. Moshapa FT, Riches-Suman K, Palmer TM. Therapeutic targeting of the proinflammatory IL-6-JAK/STAT signalling pathways responsible for vascular restenosis in type 2 diabetes mellitus. Cardiol Res Pract. 2019;2019:9846312. [Link] [DOI:10.1155/2019/9846312]
8. Ruwhof C, Van Der Laarse A. Mechanical stress-induced cardiac hypertrophy: Mechanisms and signal transduction pathways. Cardiovas Res. 2000;47(1):23-37. [Link] [DOI:10.1016/S0008-6363(00)00076-6]
9. Haghikia A, Stapel B, Hoch M, Hilfiker-Kleiner D. STAT3 and cardiac remodeling. Heart Fail Rev. 2011;16(1):35-47. [Link] [DOI:10.1007/s10741-010-9170-x]
10. Liu J, Shen Q, Wu Y. Simvastatin prevents cardiac hypertrophy in vitro and in vivo via JAK/STAT pathway. Life Sci. 2008;82(19-20):991-6. [Link] [DOI:10.1016/j.lfs.2008.02.012]
11. Youtz DJ, Isfort MC, Eichenseer CM, Nelin TD, Wold LE. In vitro effects of exercise on the heart. Life Sci. 2014;116(2):67-73. [Link] [DOI:10.1016/j.lfs.2014.08.015]
12. Rohini A, Agrawal N, Koyani CN, Singh R. Molecular targets and regulators of cardiac hypertrophy. Pharmacol Res. 2010;61(4):269-80. [Link] [DOI:10.1016/j.phrs.2009.11.012]
13. Trenerry MK, Carey KA, Ward AC, Cameron-Smith D. STAT3 signaling is activated in human skeletal muscle following acute resistance exercise. J Appl Physiol. 2007;102(4):1483-9. [Link] [DOI:10.1152/japplphysiol.01147.2006]
14. Begue G, Douillard A, Galbes O, Rossano B, Vernus B, Candau R, et al. Early activation of rat skeletal muscle IL-6/STAT1/STAT3 dependent gene expression in resistance exercise linked to hypertrophy. PLoS One. 2013;8(2):e57141. [Link] [DOI:10.1371/journal.pone.0057141]
15. Trenerry MK, Della Gatta PA, Larsen AE, Garnham AP, Cameron‐Smith D. Impact of resistance exercise training on interleukin‐6 and JAK/STAT in young men. Muscle Nerve. 2011;43(3):385-92. [Link] [DOI:10.1002/mus.21875]
16. Høydal MA, Wisløff U, Kemi OJ, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: Practical implications for exercise training. Eur J Cardiovasc Prev Rehabil. 2007;14(6):753-60. [Link] [DOI:10.1097/HJR.0b013e3281eacef1]
17. Kemi OJ, Haram PM, Loennechen JP, Osnes JB, Skomedal T, Wisløff U, et al. Moderate vs. high exercise intensity: Differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function. Cardiovasc Res. 2005;67(1):161-72. [Link] [DOI:10.1016/j.cardiores.2005.03.010]
18. Iemitsu M, Maeda S, Miyauchi T, Matsuda M, Tanaka H. Gene expression profiling of exercise‐induced cardiac hypertrophy in rats. Acta Physiologica Scandinavica. 2005;185(4):259-70. [Link] [DOI:10.1111/j.1365-201X.2005.01494.x]
19. Liu X, Xiao J, Zhu H, Wei X, Platt C, Damilano F, et al. miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell Metab. 2015;21(4):584-95. [Link] [DOI:10.1016/j.cmet.2015.02.014]
20. Passier R, Zeng H, Frey N, Naya FJ, Nicol RL, McKinsey TA, et al. CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo. J Clin Investig. 2000;105(10):1395-406. [Link] [DOI:10.1172/JCI8551]
21. Willis MS, Ike C, Li L, Wang DZ, Glass DJ, Patterson C. Muscle ring finger 1, but not muscle ring finger 2, regulates cardiac hypertrophy in vivo. Circ Res. 2007;100(4):456-9. [Link] [DOI:10.1161/01.RES.0000259559.48597.32]
22. Luckey SW, Haines CD, Konhilas JP, Luczak ED, Messmer-Kratzsch A, Leinwand LA. Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy. Exp Biol Med. 2017;242(18):1820-30. [Link] [DOI:10.1177/1535370217731503]
23. Fontana K, Oliveira HCF, Leonardo MB, Mandarim De Lacerda CA, Da Cruz‐Höfling MA. Adverse effect of the anabolic-androgenic steroid mesterolone on cardiac remodelling and lipoprotein profile is attenuated by aerobicz exercise training. Int J Exp Pathol. 2008;89(5):358-66. [Link] [DOI:10.1111/j.1365-2613.2008.00601.x]
24. De Souza MR, Pimenta L, Pithon‐Curi TC, Bucci M, Fontinele RG, De Souza RR. Effects of aerobic training, resistance training, or combined resistance‐aerobic training on the left ventricular myocardium in a rat model. Microsc Res Tech. 2014;77(9):727-34. [Link] [DOI:10.1002/jemt.22394]
25. Junqueira A, Cicogna AC, Engel LE, Aldá MA, De Tomasi LC, Giuffrida R, et al. Effects of growth hormone on cardiac remodeling during resistance training in rats. Arquivos Brasileiros De Cardiologia. 2016;106(1):18-25. [Link] [DOI:10.5935/abc.20160003]
26. Xie J, He G, Chen Q, Sun J, Dai Q, Lu J, et al. Syndecan-4 signaling is required for exercise-induced cardiac hypertrophy. Mol Med. 2016;22(1):192-201. [Link] [DOI:10.2119/molmed.2015.00026]
27. McGinnis GR, Ballmann Ch, Peters B, Nanayakkara G, Roberts M, Amin R, et al. Interleukin-6 mediates exercise preconditioning against myocardial ischemia reperfusion injury. Am J Physiol Heart Circ Physiol. 2015;308(11):H1423-33. [Link] [DOI:10.1152/ajpheart.00850.2014]
28. Sun XJ, Mao JR. Role of Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in cardioprotection of exercise preconditioning. Eur Rev Med Pharmacol Sci. 2018;22(15):4975-86. [Link]
29. Kunisada K, Negoro S, Tone E, Funamoto M, Osugi T, Yamada S, et al. Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy. Proc Natl Acad Sci U S A. 2000;97(1):315-9. [Link] [DOI:10.1073/pnas.97.1.315]
30. Hirota H, Chen J, Betz UA, Rajewsky K, Gu Y, Ross Jr J, et al. Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell. 1999;97(2):189-98. [Link] [DOI:10.1016/S0092-8674(00)80729-1]
31. Uozumi H, Hiroi Y, Zou Y, Takimoto E, Toko H, Niu P, et al. gp130 plays a critical role in pressure overload-induced cardiac hypertrophy. J Biol Chem. 2001;276(25):23115-9. [Link] [DOI:10.1074/jbc.M100814200]
32. Amooali N, Daryanoosh F, Babaee Baigi M, Mohamadi M. The impact of 12 weeks of aerobic exercise on serum levels of cardiotrophin-1, blood pressure and left ventricular hypertrophy in hypertensive elderly women. Zanjan Univ Med Sci. 2015;24(106):1-9. [Persian] [Link]
33. De Gonzalo-Calvo D, Fernández-García B, De Luxán-Delgado B, Rodríguez-González S, García-Macia M, Suárez FM, et al. Long-term training induces a healthy inflammatory and endocrine emergent biomarker profile in elderly men. Age. 2012;34(3):761-71. [Link] [DOI:10.1007/s11357-011-9266-9]
34. Limongelli G, Calabrò P, Maddaloni V, Russo A, Masarone D, D'Aponte A, et al. Cardiotrophin-1 and TNF-α circulating levels at rest and during cardiopulmonary exercise test in athletes and healthy individuals. Cytokine. 2010;50(3):245-7. [Link] [DOI:10.1016/j.cyto.2009.12.007]
35. Chen KC, Hsieh CL, Peng CC, Peng RY. Exercise rescued chronic kidney disease by attenuating cardiac hypertrophy through the cardiotrophin-1→ LIFR/gp 130→ JAK/STAT3 pathway. Eur J Prev Cardiol. 2014;21(4):507-20. [Link] [DOI:10.1177/2047487312462827]
36. Calabro P, Limongelli G, Riegler L, Maddaloni V, Palmieri R, Golia E, et al. Novel insights into the role of cardiotrophin-1 in cardiovascular diseases. J Mol Cell Cardiol. 2009;46(2):142-8. [Link] [DOI:10.1016/j.yjmcc.2008.11.002]
37. Takahashi N, Saito Y, Kuwahara K, Harada M, Tanimoto K, Nakagawa Y, et al. Hypertrophic responses to cardiotrophin-1 are not mediated by STAT3, but via a MEK5-ERK5 pathway in cultured cardiomyocytes. J Mol Cell Cardiol. 2005;38(1):185-92. [Link] [DOI:10.1016/j.yjmcc.2004.10.016]
38. McMullen JR, Shioi T, Zhang L, Tarnavski O, Sherwood MC, Kang PM, et al. Phosphoinositide 3-kinase (p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy. Proc Natl Acad Sci U S A. 2003;100(21):12355-60. [Link] [DOI:10.1073/pnas.1934654100]
39. Kodama H, Fukuda K, Pan J, Sano M, Takahashi T, Kato T, et al. Significance of ERK cascade compared with JAK/STAT and PI3-K pathway in gp130-mediated cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2000;279(4):H1635-44. [Link] [DOI:10.1152/ajpheart.2000.279.4.H1635]
40. Bueno OF, De Windt LJ, Lim HW, Tymitz KM, Witt SA, Kimball TR, et al. The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo. Circ Res. 2001;88(1):88-96. [Link] [DOI:10.1161/01.RES.88.1.88]
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