Browse > Article
http://dx.doi.org/10.5657/KFAS.2016.0807

Inhibitory Effect of Fucoidan on TGF-β1-Induced Activation of Human Pulmonary Fibroblasts  

Yim, Mi-Jin (Natural Products Research Team, National Marine Biodiversity Institute of Korea)
Lee, Dae-Sung (Natural Products Research Team, National Marine Biodiversity Institute of Korea)
Choi, Grace (Natural Products Research Team, National Marine Biodiversity Institute of Korea)
Lee, Jeong Min (Natural Products Research Team, National Marine Biodiversity Institute of Korea)
Choi, Il-Whan (Department of Microbiology and Immunology, College of Medicine Inje University)
Publication Information
Korean Journal of Fisheries and Aquatic Sciences / v.49, no.6, 2016 , pp. 807-814 More about this Journal
Abstract
Fucoidan, one of the dominant sulfated polysaccharides extracted from brown seaweed, possesses a wide range of biological activities. Transforming growth $factor-{\beta}$ ($TGF-{\beta}$) plays a pivotal role in the pathogenesis of pulmonary fibrosis, by stimulating the synthesis of profibrotic factors. In this study, we investigated the in vitro effects of fucoidan on collagen synthesis, ${\alpha}-smooth$ muscle actin (${\alpha}-SMA$) expression, and interleukin (IL)-6 production in $TGF-{\beta}$-stimulated human pulmonary fibroblasts. The expression of type I collagen and ${\alpha}-SMA$ was detected by Western blot, and the production of IL-6 by enzyme-linked immunosorbent assay. $TGF-{\beta}1$ treatment of pulmonary fibroblasts enhanced the expression of ${\alpha}-SMA$, type I collagen, and IL-6 whereas these effects were inhibited in cells pretreated with fucoidan. The activation of Smad2/3, p38 mitogen-activated protein kinases (MAPKs), and Akt was also inhibited in fucoidan-pretreated, $TGF-{\beta}1-stimulated$ human pulmonary fibroblasts. These data demonstrate the anti-fibrotic potential of fucoidan in $TGF-{\beta}-induced$ human pulmonary fibroblasts, via the inhibition of Smad2/3, p38 MAPKs, and Akt phosphorylation. Our results suggest the therapeutic potential of fucoidan in the prevention or treatment of pulmonary fibrosis.
Keywords
Fucoidan; Pulmonary fibrosis; Transforming growth $factor-{\beta}$; ${\alpha}-smooth$ muscle actin; Type I collagen;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Tanaka K, Ishihara T, Azuma A, Kudoh S, Ebina M, Nukiwa T, Sugiyama Y, Tasaka Y, Namba T, Ishihara T, Sato K, Mizushima Y and Mizushima T. 2010. Therapeutic effect of lecithinized superoxide dismutase on bleomycininduced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 298, L348-L360. http://dx.doi.org/10.1152/ajplung.00289.2009.   DOI
2 Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C and Brown RA. 2002. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3, 349-363. http://dx.doi.org/10.1038/nrm809.   DOI
3 Wang Q, Wang Y, Hyde DM, Gotwals PJ, Koteliansky VE, Ryan ST and Giri SN. 1999. Reduction of bleomycin induced lung fibrosis by transforming growth factor beta solublereceptor in hamsters. Thorax 54, 805-812.   DOI
4 Park KH, Cho EH, Kim NC and Chae HJ. 2010. Production of Fucoidan Using Marine Algae. KSBB Journal 25, 223-229.
5 Ahmed AB, Adel M, Karimi P and Peidayesh M. 2014. Pharmaceutical, cosmeceutical, and traditional applications of marine carbohydrates. Adv Food Nutr Res 73, 197-222. http://dx.doi.org/10.1016/B978-0-12-800268-1.00010-X.   DOI
6 Ahluwalia N, Shea BS and Tager AM. 2014. New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses. Am J Respir Crit Care Med 190, 867-878. http://dx.doi.org/10.1164/rccm.201403-0509PP.   DOI
7 Antoniou KM, Margaritopoulos GA and Siafakas NM. 2013. Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future. Eur Respir Rev 22, 281-291. http://dx.doi.org/10.1183/09059180.00002113.   DOI
8 Camelo A, Dunmore R, Sleeman MA and Clarke DL. 2014. The epithelium in idiopathic pulmonary fibrosis: breaking thebarrier. Front Pharmacol 4, 173. http://dx.doi.org/10.3389/fphar.2013.00173.   DOI
9 Blobe GC, Schiemann WP and Lodish HF. 2000. Role of transforming growth factor beta in human disease. N Engl J Med 342, 1350-1358. http://dx.doi.org/10.1056/NEJM200005043421807.   DOI
10 Broekelmann TJ, Limper AH, Colby TV and McDonald JA. 1991. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci U S A 88, 6642-6646.   DOI
11 Fries KM, Felch ME and Phipps RP. 1994. Interleukin-6 is an autocrine growth factor for murine lung fibroblast subsets. Am J Respir Cell Mol Biol 11, 552-560. http://dx.doi.org/10.1165/ajrcmb.11.5.7946384.   DOI
12 Cho Y, Yoon JH, Yoo JJ, Lee M, Lee DH, Cho EJ, Lee JH, Yu SJ, Kim YJ and Kim CY. 2015. Fucoidan protects hepatocytes from apoptosis and inhibits invasion of hepatocellular carcinoma by up-regulating p42/44 MAPK-dependent NDRG-1/CAP43. Acta Pharm Sin B 5, 544-553. http://dx.doi.org/10.1016/j.apsb.2015.09.004.   DOI
13 Coker RK, Laurent GJ, Shahzeidi S, HernandezRodriguez NA, Pantelidis P, du Bois RM, Jeffery PK and McAnulty RJ. 1996. Diverse cellular $TGF-{\beta}1\;and\;TGF-{\beta}3$ gene expression in normal human and murine lung. Eur Respir 9, 2501-2507.   DOI
14 Cottin V. 2016. Idiopathic interstitial pneumonias with connectivetissue diseases features: A review. Respirology 21, 245-258. http://dx.doi.org/10.1111/resp.12588.   DOI
15 Guo B, Inoki K, Isono M, Mori H, Kanasaki K, Sugimoto T, Akiba S, Sato T, Yang B, Kikkawa R, Kashiwagi A, Haneda M and Koya D. 2005. MAPK/AP-1-dependent regulation of PAI-1 gene expression by TGF-beta in rat mesangial cells. Kidney Int 68, 972-984. http://dx.doi.org/10.1111/j.1523-1755.2005.00491.x.   DOI
16 King TE, Costabel U, Cordier JF, Dopoco GA, Bois RM, Lynch D, Myers J, Panos R, Raghu G, Schwartz D and Smith CM. 2000. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161, 646-664. http://dx.doi.org/10.1164/ajrccm.161.2.ats3-00.   DOI
17 Hinz B. 2007. Formation and function of the myofibroblast during tissue repair. J Invest Dermatol 127, 526-537. http://dx.doi.org/10.1038/sj.jid.5700613.   DOI
18 Hu B, Wu Z and Phan SH. 2003. Smad3 mediates transforming growth factor-${\beta}$-induced ${\alpha}$-smooth muscle actin expression. Am J Respir Cell MolBiol 29, 397-404. http://dx.doi.org/10.1165/rcmb.2003-0063OC.   DOI
19 Jin JO, Zhang W, Du JY, Wong KW, Oda T and Yu Q. 2014. Fucoidan can function as an adjuvant in vivo to enhance dendritic cell maturation and function and promote antigenspecific T cell immune responses. PLoS One 9, e99396. http://dx.doi.org/10.1371/journal.pone.0099396.   DOI
20 Khalil N, O'Connor RN, Unruh HW, Warren PW, Flanders KC, Kemp A, Bereznay OH and Greenberg AH. 1991. Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 5, 155-162.   DOI
21 King TE Jr, Pardo A and Selman M. 2011. Idiopathic pulmonary fibrosis. Lancet 378, 1949-1961. http://dx.doi.org/10.1016/S0140-6736(11)60052-4.   DOI
22 Kuznetsova TA, Besednova NN, Somova LM and Plekhova NG. 2014. Fucoidan extracted from Fucus evanescens prevents endotoxin-induced damage in a mouse model of endotoxemia. Mar Drugs 12, 886-898. http://dx.doi.org/10.3390/md12020886.   DOI
23 Leask A and Abraham DJ. 2004. TGF-beta signaling and the fibrotic response. FASEB J 18, 816-827. http://dx.doi.org/10.1096/fj.03-1273rev.   DOI
24 Pan R, Zhang Y, Zang B, Tan L and Jin M. 2016. Hydroxysafflor yellow A inhibits TGF-${\beta}1$-induced activation of human fetal lung fibroblasts in vitro. J Pharm Pharmacol 68, 1320-1330. http://dx.doi.org/10.1111/jphp.12596.   DOI
25 Luo F, Zhuang Y, Sides MD, Sanchez CG, Shan B, White ES and Lasky JA. 2014. Arsenic trioxide inhibits transforming growth factor-${\beta}1$-induced fibroblast to myofibroblast differentiation in vitro and bleomycin induced lung fibrosis in vivo. Respir Res 15,51. http://dx.doi.org/10.1186/1465-9921-15-51.   DOI
26 Moore MW and Herzog EL. 2013. Regulation and Relevance of Myofibroblast Responses in Idiopathic Pulmonary Fibrosis. Curr Pathobiol Rep 1, 199-208. http://dx.doi.org/10.1007/s40139-013-0017-8.   DOI
27 O'Leary R, Rerek M and Wood EJ. 2004. Fucoidan modulates the effect of transforming growth factor (TGF)-beta1 on fibroblast proliferation and wound repopulation in in vitro models of dermal wound repair. Biol Pharm Bull 27, 266-270.   DOI
28 Park KY, Back JH, Hur W and Lee SY. 2007. In vitro glucose and bile acid retardation effect of fucoidan from Laminaria japonica. Kor J Biotechnol Bioeng 4, 265-269.
29 Pedroza M, Schneider DJ, Karmouty-Quintana H, Coote J, Shaw S, Corrigan R, Molina JG, Alcorn JL, Galas D, Gelinas R and Blackburn MR. 2011. Interleukin-6 contributes to inflammation and remodeling in a model of adenosine mediated lung injury. PLoS ONE 6, e22667. http://dx.doi.org/10.1371/journal.pone.0022667.   DOI
30 Raghu G, Weycker D, Edelsberg J, Bradford WZ and Oster G. 2006. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 174, 810-816. http://dx.doi.org/10.1164/rccm.200602-163OC.   DOI