Abstract
Interleukin-13 (IL-13) is associated with the production of collagen in airway remodelling of asthma. Yet, the molecular mechanisms underlying IL-13 induction of collagen remain unclear; the aim of this study is to address this issue. IL-13 dose- and time-dependently-induced collagen I production in primary cultured airway fibroblasts; this was accompanied with the STAT6 phosphorylation, and pre-treatment of cells with JAK inhibitor suppressed IL-13-induced collagen I production. Further study indicated that IL-13 stimulated JAK/STAT6-dependent PDGF production and subsequent ERK1/2 MAPK activation in airway fibroblasts, and the presence of either PDGF receptor blocker or MEK inhibitor partially suppressed IL-13-induced collagen I production. Taken together, our study suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I production in airway fibroblasts.
Similar content being viewed by others
References
Abdollahi A, Li M, Ping G, Plathow C, Domhan S, Kiessling F, Lee LB, McMahon G, et al. 2005 Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J. Exp. Med. 201 925–935
Bonner JC 2004 Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth F R 15 255–273
Bosse Y, Thompson C, Audette K, Stankova J and Rola-Pleszczynski M 2008 Interleukin-4 and interleukin-13 enhance human bronchial smooth muscle cell proliferation. Int. Arch. Allergy. Imm. 146 138–148
Chen HN, Gu XY, Liu YH, Wang J, Wirt SE, Bottino R, Schorle H, Sage J, et al. 2011a PDGF signalling controls age-dependent proliferation in pancreatic [bgr]-cells. Nature 478 349–355
Chen HH, Sun H, You FP, Sun WX, Zhou X, Chen L, Yang J, et al. 2011b Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 147 436–446
Corren J, Lemanske RF Jr, Hanania NA, Korenblat PE, Parsey MV, Arron JR, Harris JM, Scheerens H, et al. 2011 Lebrikizumab treatment in adults with asthma. New Engl. J. Med. 365 1088–1098
Elias JA and Lee CG 2011 IL-13 in asthma: the successful integration of lessons from mice and humans. Am. J. Resp. Crit. Care 183 957–958
Firszt R, Francisco D, Church TD, Thomas JM, Ingram JL and Kraft M 2014 Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma. Eur. Respir. J. 43 464–473
Halwani R, Al-Muhsen S, Al-Jahdali H and Hamid Q 2011 Role of transforming growth factor-β in airway remodeling in asthma. Am. J. Resp. Cell. Mol. 44 127–133
Halwani R, Al-Muhsen S and Hamid Q 2010 Airway remodeling in asthma. Curr. Opin. Pharmacol. 10 236–245
Hao ZM, Fan XB, Li S, Lv YF, Su HQ, Jiang HP and Li HH 2012 Vaccination with platelet-derived growth factor B kinoids inhibits CCl4-induced hepatic fibrosis in mice. J. Pharmacol. Exp. Ther. 342 835–842
Howard JD, Sarojini H, Wan R and Chien S 2014 Rapid granulation tissue regeneration by intracellular ATP delivery-A comparison with regranex. Plos One 9 91787–91791
Ingram JL, Antao-Menezes A, Mangum JB, Lyght O, Lee PJ, Elias JA and Bonner JC 2006 Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts. J. Immunol. 177 4141–4148
Ingram JL, Rice AB, Geisenhoffer K, Madtes DK and Bonner JC 2004 IL-13 and IL-1β promote lung fibroblast growth through coordinated up-regulation of PDGF-AA and PDGF-Rα. FASEB J. 18 1132–1134
Jing QP, Yin T, Wan Y, Shi HS, Luo ST, Li M, Zhang HL, He H, et al. 2012 Interleukin-13 peptide kinoid vaccination attenuates allergic inflammation in a mouse model of asthma. Int. J. Mol. Med. 30 553–560
Kim YS, Choi SJ, Choi JP, Jeon SG, Oh SY, Lee BJ, Gho YS, Lee CG, et al. 2010 IL-12-STAT4-IFN-γ axis is a key downstream pathway in the development of IL-13-mediated asthma phenotypes in a Th2 type asthma model. Exp. Mol. Med. 42 533–546
Krejci P, Prochazkova J, Bryja V, Jelinkova P, Pejchalova K, Kozubik A, Michels- Thompson L and Wilcox WR 2009 Fibroblast growth factor inhibits interferon γ-STAT1 and interleukin 6-STAT3 signaling in chondrocytes. Cell Signal. 21 151–160
Lindemann D and Racké K 2003 Glucocorticoid inhibition of interleukin-4(IL-4) and interleukin-13(IL-13) induced up-regulation of arginase in rat airway fibroblasts. N-S Arch. Pharmacol. 368 546–550
Ma Y, Halayko AJ, Basu S, Guan Q, Weiss CR, Ma AG, HayGlass KT, Becker AB, et al. 2013 Sustained suppression of IL-13 by a vaccine attenuates airway inflammation and remodeling in mice. Am. J. Resp. Cell. Mol. Biol. 48 540–549
Ostendorf T, Eitner F and Floege J 2012 The PDGF family in renal fibrosis. Pediatr. Nephrol. 27 1041–1050
Tognon C, Garnett M, Kenward E, Kay R, Morrison K and Sorensen PH 2001 The chimeric protein tyrosine kinase ETV6-NTRK3 requires both Ras-Erk1/2 and PI3-kinase-Akt signaling for fibroblast transformation. Cancer Res. 61 8909–8916
Yang G, Volk A, Petley T, Emmell E, Giles-Komar J, Shang X, Li J, Das AM, et al. 2004 Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling. Cytokine 28 224–232
Zhang L, Yang F, Li Q, Zhang X and Wang R 2011 AcSDKP inhibits the proliferation and collagen expression of cardiac fibroblasts induced by PDGF through blocking the ERK1/2 and JNK pathway activation. Int. Conf. HHBE 916–919
Zhang WX and Li CC 2011 Airway remodeling: a potential therapeutic target in asthma. World J. Pediatr. 7 124–128
Acknowledgements
This work was supported by the Natural Science Foundation of China (81070045), the Key Clinical Project for Affiliated Hospital of Ministry of Public Health of China (111).
Author information
Authors and Affiliations
Corresponding author
Additional information
Corresponding editor: Seyed E Hasnain
[Lu J, Zhu Y, Feng W, Pan Y, Li S, Han D, Liu L, Xie X, Wang G And Li M 2014 Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts. J. Biosci. 39 1–8] DOI 10.1007/s12038-014-9454-8
Rights and permissions
About this article
Cite this article
Lu, J., Zhu, Y., Feng, W. et al. Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts. J Biosci 39, 693–700 (2014). https://doi.org/10.1007/s12038-014-9454-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12038-014-9454-8