BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Baicalein and wogonin inhibit collagen deposition in SHR and WKY cardiac fibroblast cultures

  • Kong, Ebenezer K.C. (Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Huang, Yu (Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Sanderson, John E. (Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Chan, Kar-Bik (Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong) ;
  • Yu, Shan (Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong) ;
  • Yu, Cheuk-Man (Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong)
  • Published : 2010.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

In order to demonstrate the potential therapeutic effect of two flavonoids, Baicalein and Wogonin, on suppression of pathological myocardial fibrosis in hypertension, we investigated their in vitro effects on collagen expression in primary cultured cardiac fibroblasts isolated from neonatal normotensive (WKY) and hypertensive (SHR) rats. Our results showed that over-expression of collagen mRNA and protein induced in cardiac fibroblasts by angiotensin (AngII) could be attenuated significantly by both flavonoids at an optimal dosage ($30\;{\mu}M$; P < 0.01). Results of immunoblots showed that expression of 12-LO level, p-ERK/ ERK ratio and MMP-9 in AngII-stimulated SHR cardiac fibroblasts were significantly down-regulated by both flavonoids. Our results show that both Baicalein and Wogonin can suppress collagen deposition in AngII-stimulated SHR and WKY cardiac fibroblasts.

Keywords

References

  1. Yu, C. M., Tipoe, G. L., Lai, K. W. H. and Lau, C. P. (2001) Effects of combination of angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist on inflammatory cellular infiltration and myocardial interstitial fibrosis after acute myocardial infarction. J. Am. Coll. Cardiol. 38, 1207-1215 https://doi.org/10.1016/S0735-1097(01)01518-2
  2. Weber, K. T., Sun, Y., Guarda, E., Katwa, L. C., Ratajska, A., Cleutjens, J. P. and Zhou, G. (1995) Myocardial fibrosis in hypertensive heart disease: an overview of potential regulatory mechanisms. Eur. Heart J. 16(Suppl C), 24-28 https://doi.org/10.1093/eurheartj/16.suppl_C.24
  3. Weber, K. T. and Brilla, C. G. (1991) Pathological hypertrophy and cardiac interstitium. Fibrosis and renin- angiotensin-aldosterone system. Circulation 83, 1849-1865 https://doi.org/10.1161/01.CIR.83.6.1849
  4. Weber, K. T., Janicki, J. S., Shroff, S. G., Pick, R., Chen, R. M. and Bashey, R. I. (1988) Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium. Circ. Res. 62, 757-765 https://doi.org/10.1161/01.RES.62.4.757
  5. Matsubara, L. S., Matsubara, B. B., Okoshi, M. P., Franco, M. and Cicogna, A. C. (1997) Myocardial fibrosis rather than hypertrophy induces diastolic dysfunction in renovascular hypertensive rats. Can. J. Physiol. Pharmacol. 75, 1328-1334 https://doi.org/10.1139/cjpp-75-12-1328
  6. Brilla, C. G., Rupp, H., Funck, R. and Maisch, B. (1995) The renin-angiotensin-aldosterone system and myocardial collagen matrix remodelling in congestive heart failure. Eur. Heart J. 16, 107-109
  7. Murasawa, S., Mori, Y., Nozawa, Y., Gotoh, N., Shibuya, M., Masaki, H., Maruyama, K., Tsutsumi, Y., Moriguchi, Y., Shibazaki, Y., Tanaka, Y., Iwasaka, T., Inada, M. and Matsubara, H.(1998) Angiotensin II type 1 receptor-induced extracellular signal-regulated protein kinase activation is mediated by $Ca^{2+}$/calmodulin-dependent transactivation of epidermal growth factor receptor. Circ. Res. 82, 1338-1348 https://doi.org/10.1161/01.RES.82.12.1338
  8. Wen, Y., Gu, J., Liu, Y., Wang, P. H., Sun, Y. and Nadler, J. L. (2001) Overexpression of 12-lipoxygenase causes cardiac fibroblast cell growth. Circ. Res. 88, 70-76 https://doi.org/10.1161/01.RES.88.1.70
  9. Wen, Y., Nadler, J. L., Gonzales, N., Scott, S., Clauser, E. and Natarajan, R. (1996) Mechanisms of ANG II-induced mitogenic responses: role of 12-lipoxygenase and biphasic MAP kinase. Am. J. Physiol. 271, C1212-1220 https://doi.org/10.1152/ajpcell.1996.271.4.C1212
  10. Robert, V., Besse, S., Sabri, A., Silvestre, J. S., Assayag, P., Nguyen, V. T., Swynghedauw, B. and Delcayre, C. (1997) Differential regulation of matrix metalloproteinases associated with aging and hypertension in the rat heart. Lab. Invest. 76, 729-738
  11. Fedak, P. W., Verma, S., Weisel, R. D. and Li, R. K.(2005) Cardiac remodeling and failure From molecules to man (Part II). Cardiovasc. Pathol. 14, 49-60 https://doi.org/10.1016/j.carpath.2005.01.005
  12. Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L., Jr., Jones, D. W., Materson, B. J., Oparil, S., Wright, J. T., Jr. and Roccella, E. J. (2003) The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. J. Am. Med. Assoc. 289, 2560-2572 https://doi.org/10.1001/jama.289.19.2560
  13. Brilla, C. G., Matsubara, L. and Weber, K. T. (1996) Advanced hypertensive heart disease in spontaneously hypertensive rats. Lisinopril-mediated regression of myocardial fibrosis. Hypertension 28, 269-275 https://doi.org/10.1161/01.HYP.28.2.269
  14. Brilla, C. G., Matsubara, L. S. and Weber, K. T. (1993) Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J. Mol. Cell. Cardiol. 25, 563-575 https://doi.org/10.1006/jmcc.1993.1066
  15. Huang, Y., Tsang, S. Y., Yao, X. and Chen, Z. Y. (2005) Biological properties of baicalein in cardiovascular system. Curr. Drug Targets. Cardiovasc. Haematol. Disord. 5, 177-184 https://doi.org/10.2174/1568006043586206
  16. Zhang, Z. P., Wang, L. J. and Yao, Q. H. (2007) Expression of Saccharomyces cerevisiae Hem1 recombined with Arabidopsis thaliana HemA1 promoter in transgenic tobacco. Acta. Bot. Boreal.-Occident. Sin. 27, 1929-1936. (in Chinese with English abstract)
  17. Zhang, Z. P., Wang, L. J. and Yao, Q. H. (2008) Study on leaf photosynthesis and chlorophyll fluorescence of transgenic tobacco over-producing 5-aminolevulinic acid (ALA). Acta. Bot. Boreal.-Occident. Sin. 28, 1196-1202. (in Chinese with English abstract)
  18. Shimizu, I., Ma, Y. R., Mizobuchi, Y., Liu, F., Miura, T., Nakai, Y., Yasuda, M., Shiba, M., Horie, T., Amagaya, S., Kawada, N., Hori, H. and Ito, S. (1999) Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 29, 149-160 https://doi.org/10.1002/hep.510290108
  19. Ono, M., Miyamura, M., Kyotani, S., Saibara, T., Ohnishi, S. and Nishioka, Y. (1999) Effects of Sho-saiko-to extract on liver fibrosis in relation to the changes in hydroxyproline and retinoid levels of the liver in rats. J. Pharm. Pharmacol. 51, 1079-1084 https://doi.org/10.1211/0022357991773429
  20. Chen, K., Chen, J., Li, D., Zhang, X. and Mehta, J. L. (2004) Angiotensin II regulation of collagen type I expression in cardiac fibroblasts: modulation by PPAR-gamma ligand pioglitazone. Hypertension 44, 655-661 https://doi.org/10.1161/01.HYP.0000144400.49062.6b
  21. Kim, S. and Iwao, H. (2000) Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol. Rev. 52, 11-34
  22. Horiuchi, M., Akishita, M. and Dzau. V. J. (1999) Recent progress in angiotensin II type 2 receptor research in the cardiovascular system. Hypertension 33, 613-621 https://doi.org/10.1161/01.HYP.33.2.613
  23. Wang, Z. Q., Moore, A. F., Ozono, R., Siragy, H. M. and Carey, R. M. (1998) Immunolocalization of subtype 2 angiotensin II (AT2) receptor protein in rat heart. Hypertension 32, 78-83 https://doi.org/10.1161/01.HYP.32.1.78
  24. Shivakumar, K., Dostal, D. E., Boheler, K., Baker, K. M. and Lakatta, E. G. (2003) Differential response of cardiac fibroblasts from young adult and senescent rats to ANG II. Am. J. Physiol. Heart Circ. Physiol. 284, H1454-1459 https://doi.org/10.1152/ajpheart.00766.2002
  25. Schorb, W., Conrad, K. M., Singer, H. A., Dostal, D. E. and Baker, K. M. (1995) Angiotensin II is a potent stimulator of MAP-kinase activity in neonatal rat cardiac fibroblasts. J. Mol. Cell. Cardiol. 27, 1151-1160 https://doi.org/10.1016/0022-2828(95)90051-9
  26. Munshi, H. G., Wu, Y. I., Mukhopadhyay, S., Ottaviano, A. J., Sassano, A., Koblinski, J. E., Platanias, L. C. and Stack, M. S. (2004) Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK 1/2- and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-beta1-induced pericellular collagenolysis. J. Biol. Chem. 279, 39042-39050 https://doi.org/10.1074/jbc.M404958200
  27. Levick, S. P., Loch, D. C., Taylor, S. M. and Janicki, J. S. (2007) Arachidonic acid metabolism as a potential mediator of cardiac fibrosis associated with inflammation. J. Immunol. 178, 641-646 https://doi.org/10.4049/jimmunol.178.2.641
  28. Li, Y. Y., McTiernan, C. F. and Feldman, A. M. (2000) Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovasc. Res. 46, 214-224 https://doi.org/10.1016/S0008-6363(00)00003-1
  29. Vellaichamy, E., Khurana, M. L., Fink, J. and Pandey, K. N. (2005) Involvement of the NF-kappa B/matrix metalloproteinase pathway in cardiac fibrosis of mice lacking guanylyl cyclase/natriuretic peptide receptor A. J. Biol. Chem. 280, 19230-19242 https://doi.org/10.1074/jbc.M411373200
  30. Graham, H. K. and Trafford, A. W. (2007) Spatial disruption and enhanced degradation of collagen with the transition from compensated ventricular hypertrophy to symptomatic congestive heart failure. Am. J. Physiol. Heart Circ. Physiol. 292, H1364-1372 https://doi.org/10.1152/ajpheart.00355.2006
  31. Rouet-Benzineb, P., Gontero, B., Dreyfus, P. and Lafuma, C. (2000) Angiotensin II induces nuclear factor- kappa B activation in cultured neonatal rat cardiomyocytes through protein kinase C signaling pathway. J. Mol. Cell. Cardiol. 32, 1767-1778 https://doi.org/10.1006/jmcc.2000.1211
  32. Fullerton, M. J. and Funder, J. W. (1994) Aldosterone and cardiac fibrosis: in vitro studies. Cardiovasc. Res. 28, 1863-1867 https://doi.org/10.1093/cvr/28.12.1863
  33. Morales, M. O., Price, R. L. and Goldsmith, E. C. (2005) Expression of discoidin domain receptor 2 (DDR2) in the developing heart. Microsc. Microanal. 11, 260-267 https://doi.org/10.1017/S1431927605050518
  34. Miki, T., Miura, T., Nishino, Y., Yano, T., Sakamoto, J., Nakamura, Y., Ichikawa, Y., Ikeda, Y., Kobayashi, H., Ura, N. and Shimamoto, K. (2004) Granulocyte colony stimulating factor/macrophage colony stimulating factor improves postinfarct ventricular function by suppression of border zone remodelling in rats. Clin. Exp. Pharmacol. Physiol. 31, 873-882 https://doi.org/10.1111/j.1440-1681.2004.04130.x
  35. Li, Z., Tran, T. T., Ma, J. Y., O'Young, G., Kapoun, A. M., Chakravarty, S., Dugar, S., Schreiner, G. and Protter, A. A. (2004) p38 alpha mitogen-activated protein kinase inhibition improves cardiac function and reduces myocardial damage in isoproterenol-induced acute myocardial injury in rats. J. Cardiovasc. Pharmacol. 44, 486-492 https://doi.org/10.1097/01.fjc.0000141474.06383.6f
  36. Livak, K. J. and Schmittgen, T. D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402-408 https://doi.org/10.1006/meth.2001.1262
  37. Puchtler, H., Meloan, S. N. and Waldrop, F. S. (1988) Are picro-dye reactions for collagens quantitative? Chemical and histochemical considerations. Histochemistry 88, 243-256
  38. Junquiera, L. C., Junqueira, L. C. and Brentani, R. R. (1979) A simple and sensitive method for the quantitative estimation of collagen. Anal. Biochem. 94, 96-99 https://doi.org/10.1016/0003-2697(79)90795-4
  39. Yang, J., Zhang, S., Zhou, Q., Guo, H., Zhang, K., Zheng, R. and Xiao, C. (2007) PKHD1 Gene silencing may cause cell abnormal proliferation through modulation of intracellular calcium in autosomal recessive polycystic kidney disease. J. Biochem. Mol. Biol. 40, 467-474 https://doi.org/10.5483/BMBRep.2007.40.4.467

Cited by

  1. The role of mid-chain hydroxyeicosatetraenoic acids in the pathogenesis of hypertension and cardiac hypertrophy vol.90, pp.1, 2016, https://doi.org/10.1007/s00204-015-1620-8
  2. Anti-fibrotic effect of wogonin in renal tubular epithelial cells via Smad3-dependent mechanisms vol.789, 2016, https://doi.org/10.1016/j.ejphar.2016.07.014
  3. Baicalein attenuates hypertrophic scar formation via inhibition of the transforming growth factor-β/Smad2/3 signalling pathway vol.174, pp.1, 2016, https://doi.org/10.1111/bjd.14108
  4. Baicalein Attenuates Angiotensin II-Induced Cardiac Remodeling via Inhibition of AKT/mTOR, ERK1/2, NF-κB, and Calcineurin Signaling Pathways in Mice vol.28, pp.4, 2015, https://doi.org/10.1093/ajh/hpu194
  5. Therapeutic Potential of Polyphenols in Cardiac Fibrosis vol.9, pp.1663-9812, 2018, https://doi.org/10.3389/fphar.2018.00122