Abstract
Fibroblasts release prostaglandins and express a range of prostanoid receptors. However the importance of prostaglandins in fibroblast biology have not been fully explored. Our studies showed that the prostaglandin metabolite PGI2 blocks the activation of fibroblasts, antagonising the induction of Ras/MEK/ERK signalling by TGFβ. Endogenous PGI2 acts so as to limit the activation of fibroblasts following tissue injury. By contrast PGE2 induced in injured tissues or disease states may promote recruitment of inflammatory cells and lead to secondary activation of fibroblasts. The effects of PGI2 on cell signaling could be manipulated to inhibit fibrosis in patients.
Similar content being viewed by others
References
Francois H, Athirakul K, Howell D, Dash R, Mao L, Kim HS, Rockman HA, Fitzgerald GA, Koller BH (2005) Coffman TM Prostacyclin protects against elevated blood pressure and cardiac fibrosis. Cell Metab 2(3):201–207
Gilroy DW, Colville-Nash PR, McMaster S, Sawatzky DA, Willoughby DA, Lawrence T (2003) Inducible cyclooxygenase-derived 15-deoxy(Delta)12-14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and macrophage apoptosis. FASEB J 17(15):2269–2271
Jakobsson PJ, Thoren S, Morgenstern R, Samuelsson B (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci USA 96(13):7220–7225
Kamei D, Yamakawa K, Takegoshi Y et al (2004) Reduced pain hypersensitivity and inflammation in mice lacking microsomal prostaglandin e synthase-1. J Biol Chem 279(32):33684–33695
Kapoor M, McCann M, Liu S, Huh K, Denton CP, Abraham DJ, Leask A (2009) Loss of peroxisome proliferator-activated receptor gamma in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis. Arthritis Rheum 60(9):2822–2829
Kobayashi T, Narumiya S (2002) Function of prostanoid receptors: studies on knockout mice. Prostaglandins Other Lipid Mediat 68–69:557–573
Lovgren AK, Jania LA, Hartney JM, Parsons KK, Audoly LP, Fitzgerald GA, Tilley SL, Koller BH (2006) COX-2-derived prostacyclin protects against bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 291:L142–L143
McCann M, Monemdjou R, Perez G, Liu S, Shiwen X, Parapuram S, Kojima F, Denton C, Abraham D, Martel-Pelletier J, Crofford L, Leask A, Kapoor M (2010) mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis (under review, Arthritis and Rheumatism)
Moncada S, Vane JR (1978) Unstable metabolites of arachidonic acid and their role in haemostasis and thrombosis. Br Med Bull 34(2):129–135
Narumiya S (2009) Prostanoids and inflammation: a new concept arising from receptor knockout mice. J Mol Med 87(10):1015–1022, Epub 2009 J
Ricupero DA, Rishikof DC, Kuang PP, Poliks CF, Goldstein RH (1999) Regulation of connective tissue growth factor expression by prostaglandin E(2). Am J Physiol 277:1165–1171
Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271(52):33157–33160
Smyth E, Grosser T, Wang M, Yu Y, FitzGerald G (2009) Prostanoids in health and disease. J Lipid Res 50:S423–S428
Stratton R, Shiwen X, Martini G, Holmes A, Leask A, Haberberger T, Martin GR, Black CM, Abraham D (2001) Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients. J Clin Invest 108:241–250
Stratton R, Rajkumar V, Ponticos M, Nichols B, Shiwen X, Black CM, Abraham DJ, Leask A (2002) Prostacyclin derivatives prevent the fibrotic response to TGF-beta by inhibiting the Ras/MEK/ERK pathway. FASEB J 16(14):1949–1951, Epub 2002 Oct 4
Tanikawa N, Ohmiya Y, Ohkubo H et al (2002) Identification and characterization of a novel type of membrane-associated prostaglandin E synthase. Biochem Biophys Res Commun 291(4):884–889
Tanioka T, Nakatani Y, Semmyo N, Murakami M, Kudo I (2000) Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem 275(42):32775–32782
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stratton, R., Shiwen, X. Role of prostaglandins in fibroblast activation and fibrosis. J. Cell Commun. Signal. 4, 75–77 (2010). https://doi.org/10.1007/s12079-010-0089-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12079-010-0089-8