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BMC veterinary research2015; 11; 141; doi: 10.1186/s12917-015-0448-z

mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin.

Abstract: Studies in humans have shown that haemostatic and inflammatory pathways both play important roles in the pathogenesis of joint disease. The aim of this study was to assess mRNA expression of haemostatic and inflammatory factors in cultured equine fibroblast-like synoviocytes exposed to lipopolysaccharide (LPS), fibrinogen and thrombin. Synovial membranes were collected from metacarpo-phalangeal joints of 6 skeletally mature horses euthanized for non-orthopaedic reasons. Passage 4 fibroblast-like synoviocytes were left non-treated or treated with either 0.1 μg/ml LPS, 5 mg/ml fibrinogen or 5 U/ml thrombin and harvested at time points 0, 6, 24 and 48 h. mRNA expression of serum amyloid A (SAA), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), tissue factor (TF), plasminogen activator inhibitor 1 (PAI-1), urokinase plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and protease activator receptor 1 (PAR-1) was assessed using quantitative real time reverse transcriptase PCR. Results: LPS caused a significant increase in mRNA expression of SAA, IL-6, MCP-1 and uPA, and a decrease in TF, PAI-1 and PAR-1 when compared to non-treated cells. Treatment with thrombin resulted in increased mRNA expression of SAA, IL-6, MCP-1 and PAI-1, and a decreased PAR-1 expression compared to non-treated cells. The fibrinogen-treated synoviocytes showed significantly increased mRNA expression of IL-6, MCP-1, TF and PAI-1, and decreased PAR-1 expression compared to non-treated cells. Conclusions: LPS, fibrinogen and thrombin induced an increased gene expression of inflammatory markers in isolated equine fibroblast-like synoviocytes. LPS caused changes in gene expression promoting increased fibrinolysis, while fibrinogen and thrombin changed the gene expression resulting potentially in reduced fibrinolysis. Overall, it appeared that both inflammatory and haemostatic stimuli affected expression of genes involved in inflammatory and haemostatic pathways, supporting their importance in equine joint diseases.
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Publication Date: 2015-06-27 PubMed ID: 26116380PubMed Central: PMC4483216DOI: 10.1186/s12917-015-0448-zGoogle Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the study on how the exposure of equine fibroblast-like synoviocytes (a type of cell found in joints) to substances such as lipopolysaccharide (LPS), fibrinogen and thrombin influences the mRNA expression of genes involved in inflammation and blood clotting, contributing to our understanding of joint diseases in horses.

Objective and Methodology of the Research

  • The aim of the study was to explore how the exposure to LPS, fibrinogen, and thrombin impacts the mRNA expression of genes that contribute to inflammation and haemostasis (the process that causes bleeding to stop) in equine fibroblast-like synoviocytes.
  • Synovial membranes were gathered from the joints of six horses that were euthanized due to non-orthopaedic reasons. The harvested cells were exposed to specified quantities of LPS, fibrinogen and thrombin, and were then collected at different time points (0, 6, 24 and 48 hours).
  • The mRNA expression of different factors like serum amyloid A (SAA), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), tissue factor (TF), plasminogen activator inhibitor 1 (PAI-1), urokinase plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and protease activator receptor 1 (PAR-1) were assessed using a technique called quantitative real time reverse transcriptase PCR.

Findings of the Research

  • Exposure to LPS significantly increased the mRNA expression of SAA, IL-6, MCP-1 and uPA. On the contrary, it decreased the expression of TF, PAI-1 and PAR-1 as opposed to non-treated cells.
  • Thrombin treatment also resulted in increased mRNA expression of SAA, IL-6, MCP-1 and PAI-1, and a decreased expression of PAR-1 compared to non-treated cells.
  • Exposure to fibrinogen significantly increased the mRNA expression of IL-6, MCP-1, TF and PAI-1, and decreased PAR-1 expression as compared to non-treated cells.
  • Overall, the study found that LPS, fibrinogen and thrombin led to an increased gene expression of inflammatory markers in equine fibroblast-like synoviocytes. While LPS caused gene expression changes promoting increased fibrinolysis (the process of breaking down blood clots), fibrinogen and thrombin potentially led to reduced fibrinolysis.

Research Conclusions

  • The study provides evidence that both inflammatory and haemostatic stimuli influence the expression of genes involved in the inflammation and clotting pathways. These findings underscore the crucial role these pathways play in equine joint diseases.
  • These outcomes may form the basis for further research into targeted treatment options for joint diseases in horses and potentially other mammals, including humans.

Cite This Article

APA
Andreassen SM, Berg LC, Nielsen SS, Kristensen AT, Jacobsen S. (2015). mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin. BMC Vet Res, 11, 141. https://doi.org/10.1186/s12917-015-0448-z

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 11
Pages: 141

Researcher Affiliations

Andreassen, Stine Mandrup
  • Department of Large Animal Sciences, Medicine and Surgery group, University of Copenhagen, Højbakkegård allé 5, DK-2630, Tåstrup, Denmark. andreassenstine@hotmail.com.
Berg, Lise C
  • Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Dyrlægevej 16, DK-1870, Frederiksberg C, Denmark. lcb@sund.ku.dk.
Nielsen, Søren Saxmose
  • Department of Large Animal Sciences, University of Copenhagen, Grønnegårdsvej 8, DK-1870, Frederiksberg C, Denmark. saxmose@sund.ku.dk.
Kristensen, Annemarie T
  • Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Dyrlægevej 16, DK-1870, Frederiksberg C, Denmark. atk@sund.ku.dk.
Jacobsen, Stine
  • Department of Large Animal Sciences, Medicine and Surgery group, University of Copenhagen, Højbakkegård allé 5, DK-2630, Tåstrup, Denmark. stj@sund.ku.dk.

MeSH Terms

  • Animals
  • Cells, Cultured
  • Fibrinogen / pharmacology
  • Gene Expression Regulation / drug effects
  • Hemostasis / drug effects
  • Hemostasis / physiology
  • Horses
  • Inflammation / metabolism
  • Lipopolysaccharides / toxicity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Synovial Membrane / cytology
  • Thrombin / pharmacology

References

This article includes 76 references
  1. Jonsson L, Roepstorff L, Egenvall A, Nasholm A, Dalin G, Philipsson J. Prevalence of clinical findings at examinations of young Swedish warmblood riding horses.. Acta Vet Scand 2013;55:34.
    doi: 10.1186/1751-0147-55-34pmc: PMC3764978pubmed: 23597257google scholar: lookup
  2. Ireland JL, Clegg PD, McGowan CM, McKane SA, Chandler KJ, Pinchbeck GL. Disease prevalence in geriatric horses in the United Kingdom: Veterinary clinical assessment of 200 cases.. Equine Vet J 2012;44:101–6.
    doi: 10.1111/j.2042-3306.2010.00361.xpubmed: 21668494google scholar: lookup
  3. Murray RC, Walters JM, Snart H, Dyson SJ, Parkin TDH. Identification of risk factors for lameness in dressage horses.. Vet J 2010;184:27–36.
    doi: 10.1016/j.tvjl.2009.03.020pubmed: 19369100google scholar: lookup
  4. Bertone AL, Palmer JL, Jones J. Synovial fluid cytokines and eicosanoids as markers of joint disease in horses.. Vet Surg 2001;30:528–38.
    doi: 10.1053/jvet.2001.28430pubmed: 11704948google scholar: lookup
  5. McIlwraith CW. Use of synovial fluid and serum biomarkers in equine bone and joint disease: a review.. Equine Vet J 2005;37:473–82.
    doi: 10.2746/042516405774480102pubmed: 16163952google scholar: lookup
  6. Kidd JA, Barr ARS, Tarlton JF. Use of matrix metalloproteinases 2 and 9 and white blood cell counts in monitoring the treatment and predicting the survival of horses with septic arthritis.. Vet Rec 2007;161:329–34.
    doi: 10.1136/vr.161.10.329pubmed: 17827471google scholar: lookup
  7. Lindegaard C, Gleerup KB, Thomsen MH, Martinussen T, Jacobsen S, Andersen PH. Anti-inflammatory effects of intra-articular administration of morphine in horses with experimentally induced synovitis.. Am J Vet Res 2010;71:69–75.
    doi: 10.2460/ajvr.71.1.69pubmed: 20043783google scholar: lookup
  8. Ross TN, Kisiday JD, Hess T, McIlwraith CW. Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide.. Osteoarthritis Cartilage 2012;20:1583–90.
    doi: 10.1016/j.joca.2012.08.008pubmed: 22917743google scholar: lookup
  9. Kamm JL, Nixon AJ, Witte TH. Cytokine and catabolic enzyme expression in synovium, synovial fluid and articular cartilage of naturally osteoarthritic equine carpi.. Equine Vet J 2010;42:693–9.
    doi: 10.1111/j.2042-3306.2010.00140.xpmc: PMC4183755pubmed: 21039798google scholar: lookup
  10. Chang SK, Gu Z, Brenner MB. Fibroblast-like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin-11.. Immunol Rev 2010;233:256–66.
    doi: 10.1111/j.0105-2896.2009.00854.xpubmed: 20193004google scholar: lookup
  11. Briston L, Dudhia J, Lees P. Age-related differences in prostaglandin E(2) synthesis by equine cartilage explants and synoviocytes.. J Vet Pharmacol Ther 2010;33:268–76.
    doi: 10.1111/j.1365-2885.2009.01131.xpubmed: 20557444google scholar: lookup
  12. Del Rey MJ, Usategui A, Izquierdo E, Canete JD, Blanco FJ, Criado G. Transcriptome analysis reveals specific changes in osteoarthritis synovial fibroblasts.. Ann Rheum Dis 2012;71:275–80.
    pubmed: 22021863
  13. Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis.. Ann Rheum Dis 2005;64:1263–7.
    doi: 10.1136/ard.2004.025270pmc: PMC1755629pubmed: 15731292google scholar: lookup
  14. Chiu YC, Fong YC, Lai CH, Hung CH, Hsu HC, Lee TS. Thrombin-induced IL-6 production in human synovial fibroblasts is mediated by PAR1, phospholipase C, protein kinase C alpha, c-Src, NF-kappa B and p300 pathway.. Mol Immunol 2008;45:1587–99.
    doi: 10.1016/j.molimm.2007.10.004pubmed: 18062909google scholar: lookup
  15. So AK, Varisco PA, Kemkes-Matthes B, Herkenne-Morard C, Chobaz-Peclat V, Gerster JC. Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways.. J Thromb Haemost 2003;1:2510–5.
    doi: 10.1111/j.1538-7836.2003.00462.xpubmed: 14675085google scholar: lookup
  16. Armstrong S, Lees P. Effects of carprofen (R and S enantiomers and racemate) on the production of IL-1, IL-6 and TNF-alpha by equine chondrocytes and synoviocytes.. J Vet Pharmacol Ther 2002;25:145–53.
    doi: 10.1046/j.1365-2885.2002.00397.xpubmed: 12000535google scholar: lookup
  17. Busso N, Morard C, Salvi R, Peclat V, So A. Role of the tissue factor pathway in synovial inflammation.. Arthritis Rheum 2003;48:651–9.
    doi: 10.1002/art.10869pubmed: 12632417google scholar: lookup
  18. Flick MJ, LaJeunesse CM, Talmage KE, Witte DP, Palumbo JS, Pinkerton MD. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif.. J Clin Invest 2007;117:3224–35.
    doi: 10.1172/JCI30134pmc: PMC2000806pubmed: 17932565google scholar: lookup
  19. Salvi R, Peclat V, So A, Busso N. Enhanced expression of genes involved in coagulation and fibrinolysis in murine arthritis.. Arthritis Res 2000;2:504–12.
    doi: 10.1186/ar132pmc: PMC17822pubmed: 11056680google scholar: lookup
  20. Jacobsen S, Niewold TA, Halling-Thomsen M, Nanni S, Olsen E, Lindegaard C. Serum amyloid A isoforms in serum and synovial fluid in horses with lipopolysaccharide-induced arthritis.. Vet Immunol Immunopathol 2006;110:325–30.
    doi: 10.1016/j.vetimm.2005.10.012pubmed: 16337010google scholar: lookup
  21. Kitamoto Y, Nakamura E, Kudo S, Tokunaga H, Murakami E, Noguchi K. Thrombin in synovial fluid as a marker of synovial inflammation: a definite measurement by ELISA and correlation with VEGF.. Clin Chim Acta 2008;398:159–60.
    doi: 10.1016/j.cca.2008.08.009pubmed: 18765237google scholar: lookup
  22. Russell FA, McDougall JJ. Proteinase activated receptor (PAR) involvement in mediating arthritis pain and inflammation.. Inflamm Res 2009;58:119–26.
    doi: 10.1007/s00011-009-8087-0pubmed: 19184346google scholar: lookup
  23. Alturfan AA, Eralp L, Emekli N. Investigation of inflammatory and hemostatic parameters in female patients undergoing total knee arthroplasty surgery.. Inflammation 2008;31:414–21.
    doi: 10.1007/s10753-008-9093-zpubmed: 19009338google scholar: lookup
  24. Liu XF, Piela-Smith TH. Fibrin(ogen)-induced expression of ICAM-1 and chemokines in human synovial fibroblasts.. J Immunol 2000;165:5255–61.
    doi: 10.4049/jimmunol.165.9.5255pubmed: 11046059google scholar: lookup
  25. Masamune A, Kikuta K, Watanabe T, Satoh K, Hirota M, Hamada S. Fibrinogen induces cytokine and collagen production in pancreatic stellate cells.. Gut 2009;58:550–9.
    doi: 10.1136/gut.2008.154401pubmed: 19052021google scholar: lookup
  26. Sanchez-Pernaute O, Lopez-Armada MJ, Calvo E, Diez-Ortega I, Largo R, Egido J. Fibrin generated in the synovial fluid activates intimal cells from their apical surface: a sequential morphological study in antigen-induced arthritis.. Rheumatology (Oxford) 2003;42:19–25.
    doi: 10.1093/rheumatology/keg021pubmed: 12509608google scholar: lookup
  27. Ribera T, Rios J, Prades M, Monreal L, Delgado MA. Synovial fibrinolysis activity in horses with inflammatory joint/tendon sheath disease.. Annual Congress of the European College of Veterinary Surgery (ECVS), Helsinki, Finland July 2010.
  28. Ribera T, Monreal L, Delgado MA, Rios J, Prades M. Synovial fluid d-dimer concentration in horses with osteochondritis dissecans and osteoarthritis.. Vet Comp Orthop Traumatol 2013;26:54–60.
    doi: 10.3415/VCOT-11-08-0110pubmed: 23111710google scholar: lookup
  29. Haerdi-Landerer MC, Steiner A, Suter MM. Primary bovine synoviocyte cultures: A useful tool for in vitro drug testing?. Vet J 2011;188:58–63.
    doi: 10.1016/j.tvjl.2010.02.012pubmed: 20347355google scholar: lookup
  30. Upragarin N, van Asten AJAM, Tooten PCJ, Landman WJM, Gruys E. Serum amyloid A production by chicken fibroblast-like synoviocytes.. Vet Immunol Immunopathol 2005;106:39–51.
    doi: 10.1016/j.vetimm.2005.01.004pubmed: 15910991google scholar: lookup
  31. Santangelo KS, Johnson AL, Ruppert AS, Bertone AL. Effects of hyaluronan treatment on lipopolysaccharide-challenged fibroblast-like synovial cells.. Arthritis Res Ther 2007;9:R1.
    doi: 10.1186/ar2104pmc: PMC1860057pubmed: 17214881google scholar: lookup
  32. Busso N, Peclat V, So A, Sappino AP. Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints.. Ann Rheum Dis 1997;56:550–7.
    doi: 10.1136/ard.56.9.550pmc: PMC1752434pubmed: 9370880google scholar: lookup
  33. Esmon CT. The impact of the inflammatory response on coagulation.. Thromb Res 2004;114:321–7.
    doi: 10.1016/j.thromres.2004.06.028pubmed: 15507261google scholar: lookup
  34. Frisbie DD, Al-Sobayil F, Billinghurst RC, Kawcak CE, McIlwraith CW. Changes in synovial fluid and serum biomarkers with exercise and early osteoarthritis in horses.. Osteoarthritis Cartilage 2008;16:1196–204.
    doi: 10.1016/j.joca.2008.03.008pubmed: 18442931google scholar: lookup
  35. van den Boom R, van der Harst MR, Brommer H, Brama PA, Barneveld A, van Weeren PR. Relationship between synovial fluid levels of glycosaminoglycans, hydroxyproline and general MMP activity and the presence and severity of articular cartilage change on the proximal articular surface of P1.. Equine Vet J 2005;37:19–25.
    doi: 10.2746/0425164054406919pubmed: 15651729google scholar: lookup
  36. Ribera T, Monreal L, Armengou L, Rios J, Prades M. Synovial fluid d-dimer concentration in foals with septic joint disease.. J Vet Intern Med 2011;25:1113–7.
    doi: 10.1111/j.1939-1676.2011.0758.xpubmed: 21781162google scholar: lookup
  37. Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease.. Semin Immunopathol 2012;34:43–62.
    doi: 10.1007/s00281-011-0290-8pubmed: 22037947google scholar: lookup
  38. Hoppe B, Dorner T. Coagulation and the fibrin network in rheumatic disease: a role beyond haemostasis.. Nat Rev Rheumatol 2012;8:738–46.
    doi: 10.1038/nrrheum.2012.184pubmed: 23147903google scholar: lookup
  39. Ogura N, Satoh K, Akutsu M, Tobe M, Kuyama K, Kuboyama N. MCP-1 production in temporomandibular joint inflammation.. J Dent Res 2010;89:1117–22.
    doi: 10.1177/0022034510376041pubmed: 20647497google scholar: lookup
  40. Ovlisen K, Kristensen AT, Jensen AL, Tranholm M. IL-1 beta, IL-6, KC and MCP-1 are elevated in synovial fluid from haemophilic mice with experimentally induced haemarthrosis.. Haemophilia 2009;15:802–10.
    doi: 10.1111/j.1365-2516.2008.01973.xpubmed: 19444976google scholar: lookup
  41. Villiger PM, Terkeltaub R, Lotz M. Production of monocyte chemoattractant protein-1 by inflamed synovial tissue and cultured synoviocytes.. J Immunol 1992;149:722–7.
    pubmed: 1624809
  42. Harigai M, Hara M, Yoshimura T, Leonard EJ, Inoue K, Kashiwazaki S. Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium.. Clin Immunol Immunop 1993;69:83–91.
    doi: 10.1006/clin.1993.1153pubmed: 8403545google scholar: lookup
  43. Colotta F, Sciacca FL, Sironi M, Luini W, Rabiet MJ, Mantovani A. Expression of monocyte chemotactic protein-1 by monocytes and endothelial-cells exposed to thrombin.. Am J Pathol 1994;144:975–85.
    pmc: PMC1887349pubmed: 8178946
  44. Harley SL, Powell JT. Fibrinogen up-regulates the expression of monocyte chemoattractant protein 1 in human saphenous vein endothelial cells.. Biochem J 1999;341:739–44.
    doi: 10.1042/0264-6021:3410739pmc: PMC1220413pubmed: 10417339google scholar: lookup
  45. Seeger FH, Blessing E, Gu L, Bornhold R, Denger S, Kreuzer J. Fibrinogen induces chemotactic activity in endothelial cells.. Acta Physiol Scand 2002;176:109–15.
    doi: 10.1046/j.1365-201X.2002.01023.xpubmed: 12354170google scholar: lookup
  46. Barton MH, Collatos C, Moore JN. Endotoxin induced expression of tumour necrosis factor, tissue factor and plasminogen activator inhibitor activity by peritoneal macrophages.. Equine Vet J 1996;28:382–9.
    doi: 10.1111/j.2042-3306.1996.tb03109.xpubmed: 8894536google scholar: lookup
  47. Hoffman M, Monroe DM. A cell-based model of hemostasis.. Thromb Haemost 2001;85:958–65.
    pubmed: 11434702
  48. Busso N, Hamilton JA. Extravascular coagulation and the plasminogen activator/plasmin system in rheumatoid arthritis.. Arthritis Rheum 2002;46:2268–79.
    doi: 10.1002/art.10498pubmed: 12355473google scholar: lookup
  49. Bokarewa MI, Morrissey JH, Tarkowski A. Tissue factor as a proinflammatory agent.. Arthritis Res 2002;4:190–5.
    doi: 10.1186/ar405pmc: PMC111021pubmed: 12010569google scholar: lookup
  50. Nonaka T, Kikuchi H, Ikeda T, Okamoto Y, Hamanishi C, Tanaka S. Hyaluronic acid inhibits the expression of u-PA, PAI-1, and u-PAR in human synovial fibroblasts of osteoarthritis and rheumatoid arthritis.. J Rheumatol 2000;27:997–1004.
    pubmed: 10782829
  51. Alpay Z, Saed GM, Diamond MP. Postoperative adhesions: from formation to prevention.. Semin Reprod Med 2008;26:313–21.
    doi: 10.1055/s-0028-1082389pubmed: 18756408google scholar: lookup
  52. Levi M, van der Poll T. Two-way interactions between inflammation and coagulation.. Trends Cardiovasc Med 2005;15:254–9.
    doi: 10.1016/j.tcm.2005.07.004pubmed: 16226680google scholar: lookup
  53. Yang YH, Hall P, Little CB, Fosang AJ, Milenkovski G, Santos L. Reduction of arthritis severity in protease-activated receptor-deficient mice.. Arthritis Rheum 2005;52:1325–32.
    doi: 10.1002/art.21001pubmed: 15818676google scholar: lookup
  54. Furuhashi I, Abe K, Sato T, Inoue H. Thrombin-stimulated proliferation of cultured human synovial fibroblasts through proteolytic activation of proteinase-activated receptor-1.. J Pharmacol Sci 2008;108:104–11.
    doi: 10.1254/jphs.08126FPpubmed: 18787303google scholar: lookup
  55. Hirano F, Kobayashi A, Hirano Y, Nomura Y, Fukawa E, Makino I. Thrombin-induced expression of RANTES mRNA through protease activated receptor-1 in human synovial fibroblasts.. Ann Rheum Dis 2002;61:834–7.
    doi: 10.1136/ard.61.9.834pmc: PMC1754231pubmed: 12176812google scholar: lookup
  56. Lang R, Song PI, Legat FJ, Lavker RM, Harten B, Kalden H. Human corneal epithelial cells express functional PAR-1 and PAR-2.. Invest Ophthalmol Vis Sci 2003;44:99–105.
    doi: 10.1167/iovs.02-0357pubmed: 12506061google scholar: lookup
  57. Mbebi C, Rohn T, Doyennette MA, Chevessier F, Jandrot-Perrus M, Hantai D. Thrombin receptor induction by injury-related factors in human skeletal muscle cells.. Exp Cell Res 2001;263:77–87.
    doi: 10.1006/excr.2000.5090pubmed: 11161707google scholar: lookup
  58. Zhao AP, Dawson H, Urban JF, Finkelman FD, Shea-Donohue T. Up-regulation of PAR-1 and PAR-2 expression contributes to nematode-induced hypercontractility of murine intestinal smooth muscle.. Gastroenterol 2003;124:A89–9.
    doi: 10.1016/S0016-5085(03)80438-9google scholar: lookup
  59. Ellis CA, Tiruppathi C, Sandoval R, Niles WD, Malik AB. Time course of recovery of endothelial cell surface thrombin receptor (PAR-1) expression.. Am J Physiol 1999;276:C38–45.
    pubmed: 9886918
  60. Pompili E, Fabrizi C, Fumagalli L. PAR-1 upregulation by trimethyltin and lipopolysaccharide in cultured rat astrocytes.. Int J Mol Med 2006;18:33–9.
    pubmed: 16786153
  61. Rohatgi T, Henrich-Noack P, Sedehizade F, Goertler M, Wallesch CW, Reymann KG. Transient focal ischemia in rat brain differentially regulates mRNA expression of protease-activated receptors 1 to 4.. J Neurosci Res 2004;75:273–9.
    doi: 10.1002/jnr.10847pubmed: 14705148google scholar: lookup
  62. Yan W, Tiruppathi C, Qiao R, Lum H, Malik AB. Tumor necrosis factor decreases thrombin receptor expression in endothelial cells.. J Cell Physiol 1996;166:561–7.
    doi: 10.1002/(SICI)1097-4652(199603)166:3<561::AID-JCP10>3.0.CO;2-Apubmed: 8600159google scholar: lookup
  63. Yoo SA, Kwok SK, Kim WU. Proinflammatory role of vascular endothelial growth factor in the pathogenesis of rheumatoid arthritis: prospects for therapeutic intervention.. Med Inflam 2008;2008:129873.
    pmc: PMC2638142pubmed: 19223981
  64. Lee SS, Joo YS, Kim WU, Min DJ, Min JK, Park SH. Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis.. Clin Exp Rheumatol 2001;19:321–4.
    pubmed: 11407088
  65. Ludin A, Sela JJ, Schroeder A, Samuni Y, Nitzan DW, Amir G. Injection of vascular endothelial growth factor into knee joints induces osteoarthritis in mice.. Osteoarthritis Cartilage 2013;21:491–7.
    doi: 10.1016/j.joca.2012.12.003pubmed: 23257244google scholar: lookup
  66. Jansen H, Meffert RH, Birkenfeld F, Petersen W, Pufe T. Detection of vascular endothelial growth factor (VEGF) in moderate osteoarthritis in a rabbit model.. Ann Anat 2012;194:452–6.
    doi: 10.1016/j.aanat.2012.01.006pubmed: 22429866google scholar: lookup
  67. Kim CO, Huh AJ, Kim MS, Chin BS, Han SH, Choi SH. LPS-induced vascular endothelial growth factor expression in rat lung pericytes.. Shock 2008;30:92–7.
    pubmed: 18562929
  68. Shiose S, Hata Y, Noda Y, Sassa Y, Takeda A, Yoshikawa H. Fibrinogen stimulates in vitro angiogenesis by choroidal endothelial cells via autocrine VEGF.. Graef Arch Clin Exp 2004;242:777–83.
    doi: 10.1007/s00417-004-0910-2pubmed: 15103470google scholar: lookup
  69. Huang YQ, Li JJ, Hu L, Lee M, Karpatkin S. Thrombin induces increased expression and secretion of VEGF from human FS4 fibroblasts, DU145 prostate cells and CHRF megakaryocytes.. Tromb Haemost 2001;86:1094–8.
    pubmed: 11686329
  70. Guo F, Liu J, Wang C, Liu N, Lu P. Fibrinogen, fibrin, and FDP induce C-reactive protein generation in rat vascular smooth muscle cells: pro-inflammatory effect on atherosclerosis.. Biochem Bioph Res Co 2009;390:942–6.
    doi: 10.1016/j.bbrc.2009.10.082pubmed: 19852936google scholar: lookup
  71. Lu PP, Liu JT, Liu N, Guo F, Ji YY, Pang XM. Pro-inflammatory effect of fibrinogen and FDP on vascular smooth muscle cells by IL-6, TNF-alpha and iNOS.. Life Sci 2011;88:839–45.
    doi: 10.1016/j.lfs.2011.03.003pubmed: 21439977google scholar: lookup
  72. Haneda S, Nagaoka K, Nambo Y, Kikuchi M, Nakano Y, Matsui M. Interleukin-1 receptor antagonist expression in the equine endometrium during the peri-implantation period.. Domest Anim Endocrin 2009;36:209–18.
    doi: 10.1016/j.domaniend.2008.11.006pubmed: 19157767google scholar: lookup
  73. Deschene K, Celeste C, Boerboom D, Theoret CL. Constitutive expression of hypoxia-inducible factor-1 alpha in keratinocytes during the repair of skin wounds in horses.. Wound Repair Regen 2011;19:250–9.
    doi: 10.1111/j.1524-475X.2010.00663.xpubmed: 21362093google scholar: lookup
  74. Iqbal J, Bird JL, Hollander AP, Bayliss MT. Effect of matrix depleting agents on the expression of chondrocyte metabolism by equine chondrocytes.. Res Vet Sci 2004;77:249–56.
    doi: 10.1016/j.rvsc.2004.04.005pubmed: 15276777google scholar: lookup
  75. Tellmann GG. O: LightCycler® 480 Real-Time PCR system: Innovative solutions for relative quantification.. Biochemica 2006;4:16–7.
  76. . R: A language and environment for statistical computing [http://www.R-project.org]. .
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