Role of Prostaglandins in Fibroblast Activation and Fibrosis

Overview

Journal J Cell Commun Signal

Date 2010 Jun 10

PMID 20531982

Citations 17

Authors

Richard Stratton

Xu Shiwen

Affiliations

Soon will be listed here.

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 PGI(2) blocks the activation of fibroblasts, antagonising the induction of Ras/MEK/ERK signalling by TGFbeta. Endogenous PGI(2) acts so as to limit the activation of fibroblasts following tissue injury. By contrast PGE(2) induced in injured tissues or disease states may promote recruitment of inflammatory cells and lead to secondary activation of fibroblasts. The effects of PGI(2) on cell signaling could be manipulated to inhibit fibrosis in patients.

Citing Articles

Embryo-derive TNF promotes decidualization via fibroblast activation.

Chen S, Shi W, Lin Y, Yang Z, Wang Y, Li M Elife. 2023; 12.

PMID: 37458359 PMC: 10374279. DOI: 10.7554/eLife.82970.

Dipotassium Glycyrrhizininate Improves Skin Wound Healing by Modulating Inflammatory Process.

Leite C, Bonafe G, Pires O, Santos T, Pereira G, Pereira J Int J Mol Sci. 2023; 24(4).

PMID: 36835248 PMC: 9965141. DOI: 10.3390/ijms24043839.

Prostacyclin Released by Cancer-Associated Fibroblasts Promotes Immunosuppressive and Pro-Metastatic Macrophage Polarization in the Ovarian Cancer Microenvironment.

Sommerfeld L, Knuth I, Finkernagel F, Pesek J, Nockher W, Jansen J Cancers (Basel). 2022; 14(24).

PMID: 36551640 PMC: 9776493. DOI: 10.3390/cancers14246154.

Arachidonate 5-lipoxygenase is essential for biosynthesis of specialized pro-resolving mediators and cardiac repair in heart failure.

Halade G, Kain V, Hossain S, Parcha V, Limdi N, Arora P Am J Physiol Heart Circ Physiol. 2022; 323(4):H721-H737.

PMID: 36018758 PMC: 9529265. DOI: 10.1152/ajpheart.00115.2022.

Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states.

Jaber M, Radwan A, Loyfer N, Abdeen M, Sebban S, Khatib A Nat Commun. 2022; 13(1):3475.

PMID: 35715410 PMC: 9205865. DOI: 10.1038/s41467-022-31131-8.

References

Jakobsson P, Thoren S, Morgenstern R, Samuelsson B . Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A. 1999; 96(13):7220-5. PMC: 22058. DOI: 10.1073/pnas.96.13.7220. View

Kapoor M, McCann M, Liu S, Huh K, Denton C, Abraham D . Loss of peroxisome proliferator-activated receptor gamma in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis. Arthritis Rheum. 2009; 60(9):2822-9. DOI: 10.1002/art.24761. View

Tanioka T, Nakatani Y, Semmyo N, Murakami M, Kudo I . Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem. 2000; 275(42):32775-82. DOI: 10.1074/jbc.M003504200. View

Ricupero D, Rishikof D, Kuang P, Poliks C, Goldstein R . Regulation of connective tissue growth factor expression by prostaglandin E(2). Am J Physiol. 1999; 277(6):L1165-71. DOI: 10.1152/ajplung.1999.277.6.L1165. View

Kobayashi T, Narumiya S . Function of prostanoid receptors: studies on knockout mice. Prostaglandins Other Lipid Mediat. 2002; 68-69:557-73. DOI: 10.1016/s0090-6980(02)00055-2. View

Francois H, Athirakul K, Howell D, Dash R, Mao L, Kim H . Prostacyclin protects against elevated blood pressure and cardiac fibrosis. Cell Metab. 2005; 2(3):201-7. DOI: 10.1016/j.cmet.2005.08.005. View

Gilroy D, Colville-Nash P, McMaster S, Sawatzky D, Willoughby D, Lawrence T . Inducible cyclooxygenase-derived 15-deoxy(Delta)12-14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and macrophage apoptosis. FASEB J. 2003; 17(15):2269-71. DOI: 10.1096/fj.02-1162fje. View

Stratton R, Rajkumar V, Ponticos M, Nichols B, Shiwen X, Black C . Prostacyclin derivatives prevent the fibrotic response to TGF-beta by inhibiting the Ras/MEK/ERK pathway. FASEB J. 2002; 16(14):1949-51. DOI: 10.1096/fj.02-0204fje. View

Stratton R, Shiwen X, Martini G, Holmes A, Leask A, Haberberger T . Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients. J Clin Invest. 2001; 108(2):241-50. PMC: 203022. DOI: 10.1172/JCI12020. View

10.

Tanikawa N, Ohmiya Y, Ohkubo H, Hashimoto K, Kangawa K, Kojima M . Identification and characterization of a novel type of membrane-associated prostaglandin E synthase. Biochem Biophys Res Commun. 2002; 291(4):884-9. DOI: 10.1006/bbrc.2002.6531. View

11.

Moncada S, Vane J . Unstable metabolites of arachidonic acid and their role in haemostasis and thrombosis. Br Med Bull. 1978; 34(2):129-35. DOI: 10.1093/oxfordjournals.bmb.a071482. View

12.

Lovgren A, Jania L, Hartney J, Parsons K, Audoly L, FitzGerald G . COX-2-derived prostacyclin protects against bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2006; 291(2):L144-56. DOI: 10.1152/ajplung.00492.2005. View

13.

Smith W, Garavito R, Dewitt D . Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem. 1996; 271(52):33157-60. DOI: 10.1074/jbc.271.52.33157. View

14.

Kamei D, Yamakawa K, Takegoshi Y, Mikami-Nakanishi M, Nakatani Y, Oh-Ishi S . Reduced pain hypersensitivity and inflammation in mice lacking microsomal prostaglandin e synthase-1. J Biol Chem. 2004; 279(32):33684-95. DOI: 10.1074/jbc.M400199200. View

15.

Smyth E, Grosser T, Wang M, Yu Y, FitzGerald G . Prostanoids in health and disease. J Lipid Res. 2008; 50 Suppl:S423-8. PMC: 2674745. DOI: 10.1194/jlr.R800094-JLR200. View

16.

Narumiya S . Prostanoids and inflammation: a new concept arising from receptor knockout mice. J Mol Med (Berl). 2009; 87(10):1015-22. DOI: 10.1007/s00109-009-0500-1. View

17.

McCann M, Monemdjou R, Ghassemi-Kakroodi P, Fahmi H, Perez G, Liu S . mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis. Arthritis Res Ther. 2011; 13(1):R6. PMC: 3546456. DOI: 10.1186/ar3226. View