대한의용생체공학회:의공학회지 (Journal of Biomedical Engineering Research)

  • 제39권4호
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  • Pages.168-174
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  • 2018
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  • 1229-0807(pISSN)
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  • 2288-9396(eISSN)
대한의용생체공학회 (The Korean Society of Medical and Biological Engineering)
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유체전단응력에 의하여 3T3-L1 지방세포가 받는 영향

Effects of Fluid Shear Stress on 3T3-L1 Preadipocytes

  • 이정근 (연세대학교 보건과학대학 의공학부) ;
  • 이영훈 (연세대학교 보건과학대학 의공학부) ;
  • 진희원 (연세대학교 보건과학대학 의공학부) ;
  • 이서현 (연세대학교 보건과학대학 의공학부) ;
  • 김지현 (연세대학교 보건과학대학 의공학부)
  • Lee, Jeongkun (Department of Biomedical Engineering, Yonsei University) ;
  • Lee, Yeong Hun (Department of Biomedical Engineering, Yonsei University) ;
  • Jin, Heewon (Department of Biomedical Engineering, Yonsei University) ;
  • Lee, Seohyun (Department of Biomedical Engineering, Yonsei University) ;
  • Kim, Chi Hyun (Department of Biomedical Engineering, Yonsei University)
  • 투고 : 2018.06.18
  • 심사 : 2018.08.24
  • 발행 : 2018.08.31
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초록

Adipocytes affect obesity through the regulation of lipid metabolism. Physical loading is an important regulator of fat tissue. There are ongoing in vitro studies inducing mechanotransduction on 3T3-L1 preadipocytes with mechanical stimulus in order to treat obesity by inhibiting adipogenesis and provoking cell death. In this study, our goal was to suggest a new therapy for obesity by investigating whether fluid shear stress (FSS) changes transcription factors on 3T3-L1 related with adipogenesis and cell death. FSS loading was applied to 3T3-L1 preadipocytes at 1Pa and 1Hz. After loading, bright field images were taken and an immunofluorescence assay was conducted to observe actin stress fiber formation. Western blot analysis was conducted to identify the activation of the ERK pathway as well as the adipogenic factors, which including C/EBPs and $PPAR{\gamma}$. The expression of osteopontin, a protein related to inflammation in adipose tissue, and cell death related factors, Bax, Bcl-2, and Beclin, were also measured. Results showed that FSS stimulated the formation of actin stress fibers in 3T3-L1 and also that the activation of C/EBPs decreased significantly when compared with the control group. $PPAR{\gamma}$ activation in the 2 hour FSS group was lower than the 1 hour FSS group, which implied that the results were time dependent. Additionally, there were no differences in the expression of cell death factors after FSS loading. In summary, similar to other fibroblasts, the formation of actin stress fibers induced by mechanotransduction may affect the differentiation of 3T3-L1, leading to inhibition of adipogenesis and inflammation.

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참고문헌

  1. B.M. Spiegelman and J.S. Flier, "Obesity and the regulation of energy balance," cell, vol. 104, no. 4, pp. 531-543, 2001. https://doi.org/10.1016/S0092-8674(01)00240-9
  2. X. Formiguera and A. Canton, "Obesity: epidemiology and clinical aspects," Best Pract. Res. Clin. Gastroenterol., vol. 18, no. 6, pp. 1125-1146, 2004. https://doi.org/10.1016/S1521-6918(04)00091-5
  3. C. Weyer, J.E. Foley, C. Bogardus, P.A. Tataranni, and R.E. Pratley, "Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance," Diabetologia, vol. 43, no. 12, pp. 1498-1506, 2000. https://doi.org/10.1007/s001250051560
  4. Y.W. Wang and P.J.H. Jones, "Conjugated linoleic acid and obesity control: efficacy and mechanisms," Int. J. Obes., vol. 28, no. 8, pp. 941-955, 2004. https://doi.org/10.1038/sj.ijo.0802641
  5. C.L. Hsu and G.C. Yen, "Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells," J. Agric. Food Chem., vol. 55, no. 5, pp. 1730-1736, 2007. https://doi.org/10.1021/jf062912b
  6. D. Hwang, S. Kim, H. Lee, S. Lee, D. Seo, S. Cho, S. Chen, T. Han, and H.S. Kim, "The Effects of Whole Body Vibration in the Aspect of Reducing Abdominal Adipose Tissue in High-Fat Diet Mice Model," J. Biomed. Eng. Res., vol. 38, no. 1, pp. 49-55, 2017. https://doi.org/10.9718/JBER.2017.38.1.49
  7. M.I. Lefterova, and M.A. Lazar, "New developments in adipogenesis," Trends Endocrinol. Metab., vol. 20, no. 3, pp. 107-114, 2009. https://doi.org/10.1016/j.tem.2008.11.005
  8. U.A. White, and J.M. Stephens, "Transcriptional factors that promote formation of white adipose tissue," Mol. Cell. Endocrinol., vol. 318, no. 1-2, pp. 10-14, 2010. https://doi.org/10.1016/j.mce.2009.08.023
  9. K. Vermeulen, D.R.V Bockstaele, and Z.N. Berneman, "Apoptosis: mechanisms and relevance in cancer," Ann. Hematol., vol. 84, no.10, pp. 627-639, 2005. https://doi.org/10.1007/s00277-005-1065-x
  10. M.O. Hengartner, "The biochemistry of apoptosis," Nature, vol. 407, pp. 770-776, 2000. https://doi.org/10.1038/35037710
  11. N. Shoham, and A. Gefen, "Mechanotransduction in adipo-cytes," J. Biomech., vol. 45, no. 1, pp. 1-8, 2012. https://doi.org/10.1016/j.jbiomech.2011.10.023
  12. R. McBeath, D.M. Pirone, C.M. Nelson, K. Bhadriraju, and C.S. Chen, "Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment," Dev. Cell, vol. 6, no. 4, pp. 483-495, 2004. https://doi.org/10.1016/S1534-5807(04)00075-9
  13. S. Tojkander, G. Gateva, and P. Lappalainen, "Actin stress fibers-assembly, dynamics and biological roles," J. Cell Sci., vol. 125, no. 8, pp. 1855-1864, 2012. https://doi.org/10.1242/jcs.098087
  14. Y. Hara, S. Wakino, Y. Tanabe, M. Saito, H. Tokuyama, N. Washida, S. Tatematsu, K. Yoshioka, K. Homma, K. Hasegawa, H. Minakuchi, K. Fujimura, K. Hosoya, K. Hayashi, K. Nakayama, and H. Itoh, "Rho and Rho-kinase activity in adipocytes contributes to a vicious cycle in obesity that may involve mechanical stretch," Sci. Signal., vol. 4, no. 157, pp. ra3, 2011. https://doi.org/10.1126/scisignal.2001227
  15. Y. Tanabe, M. Koga, M. Saito, Y. Matsunaga, and K. Nakayama, "Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of $PPAR{\gamma}2$," J. Cell. Sci., vol. 117, no. 16, pp. 3605-3614, 2004. https://doi.org/10.1242/jcs.01207
  16. Y. Tanabe, Y. Matsunaga, M. Saito, and K. Nakayama, "Involvement of cyclooxygenase-2 in synergistic effect of cyclic stretching and eicosapentaenoic acid on adipocyte differentiation," J. Pharmacol. Sci., vol. 106, no. 3, pp. 478-484, 2008. https://doi.org/10.1254/jphs.FP0071886
  17. M.H. Kroll, J.D. Hellums, L.y V. Mclntire, A.I. Schafer, and J.L. Moake, "Platelets and shear stress," Blood, vol. 88, no .5, pp. 1525-1541, 1996.
  18. Y. Li, J. Yuan, Q. Wang, L. Sun, Y. Sha, Y. Li, L. Wang, and Z. Wang, "The collective influence of 1, 25-dihydroxyvitamin D3 with physiological fluid shear stress on osteoblasts," Steroids, vol. 129, pp. 9-16, 2016.
  19. P. Wang, P.P. Guan, C. Guo, F. Zhu, K. Konstantopoulos, and Z.Y. Wang, "Fluid shear stress-induced osteoarthritis: roles of cyclooxygenase-2 and its metabolic products in inducing the expression of proinflammatory cytokines and matrix metalloproteinases," FASEB J., vol. 27, no. 12, pp. 4664-4677, 2013. https://doi.org/10.1096/fj.13-234542
  20. T.M. Maul, D.W. Chew, A. Nieponice, and D.A. Vorp, "Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation," Biomech. Model. Mechanobiol., vol. 10, no. 6, pp. 939-953, 2011. https://doi.org/10.1007/s10237-010-0285-8
  21. H. Huang, R.D. Kamm, and R.T. Lee, "Cell mechanics and mechanotransduction:pathways, probes, and physiology," Am. J. Physiol. Cell. Physiol., vol. 287, no. 1, pp. C1-C11, 2004. https://doi.org/10.1152/ajpcell.00559.2003
  22. C.H. Kim, L. You, C.E. Yellowley, and C.R. Jacobs, "Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling," Bone, vol. 39, no. 5, pp. 1043-1047, 2006. https://doi.org/10.1016/j.bone.2006.05.017
  23. C.H. Kim, and Y.M. Yoo, "Fluid shear stress and melatonin in combination activate anabolic proteins in MC3T3-E1 osteoblast cells," J. Pineal Res., vol. 54, no. 4, pp. 453-461, 2013. https://doi.org/10.1111/jpi.12043
  24. K. Kumawat, T. Koopmans, M.H. Menzen, A. Prins, M. Smit, A.J. Halayko, and R. Gosens, "Cooperative signaling by TGF-T${\beta}1$ and WNT-11 drives sm-${\alpha}$-actin expression in smooth muscle via Rho kinase-actin-MRTF-A signaling," Am. J. Physiol. Lung Cell. Mol. Physiol., vol. 311, no. 3, pp. L529-L537, 2016. https://doi.org/10.1152/ajplung.00387.2015
  25. Y. Bannai, L.R. Aminova, M.J. Faulkner, M. Ho, and B.A. Wilson, "Rho/ROCK-dependent inhibition of 3T3-L1 adipogenesis by G-protein-deamidating dermonecrotic toxins: differential regulation of Notch1, Pref1/Dlk1, and ${\beta}$-catenin signaling," Front. Cell. Infect. Microbiol., vol. 2, pp. 80, 2012.
  26. D.T.V. Diep, K. Hong, T. Khun, M. Zheng, A. Ul-Haq, H.S. Jun, Y.B. Kim, and K.H. Chun, "Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells," Sci. Rep., vol. 8, no. 1, pp. 2477, 2018. https://doi.org/10.1038/s41598-018-20821-3
  27. T. Horii, S. Morita, M. Kimura, and I. Hatada, "Epigenetic regulation of adipocyte differentiation by a Rho guanine nucleotide exchange factor, WGEF," PLoS One., vol. 4, no. 6, pp. e5809, 2009. https://doi.org/10.1371/journal.pone.0005809
  28. N.J. Turner, H.S. Jones, J.E. Davies, and A.E. Canfield, "Cyclic stretch-induced $TGF{\beta}1$/Smad signaling inhibits adipogenesis in umbilical cord progenitor cells," Biochem. Biophys. Res. Commun., vol. 377, no. 4, pp. 1147-1151, 2008. https://doi.org/10.1016/j.bbrc.2008.10.131
  29. M.G. Hossain, T. Iwata, N. Mizusawa, S.W. Shima, T. Okutsu, K. Ishimoto, and K. Yoshimoto, "Compressive force inhibits adipogenesis hrough COX-2-mediated down-regulation of PPARgamma2 and C/EBPalpha," J. Biosci. Bioeng., vol. 109, no. 3, pp. 297-303, 2010. https://doi.org/10.1016/j.jbiosc.2009.09.003
  30. Y.H. Lee, A.P. Petkova, and J.G. Granneman, "Identification of an adipogenic niche for adipose tissue remodeling and restoration," Cell metab., vol. 18, no. 3, pp. 355-367, 2013. https://doi.org/10.1016/j.cmet.2013.08.003
  31. M. Zeyda, K. Gollinger, J. Todoric, F.W. Kiefer, M. Keck, O. Aszmann, G. Prager, G.J. Zlabinger, P. Petzelbauer, and T.M. stulnig, "Osteopontin is an activator of human adipose tissue macrophages and directly affects adipocyte function," Endocrinology, vol. 152, no. 6, pp. 2219-2227, 2011. https://doi.org/10.1210/en.2010-1328