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前列腺素E_2抑制转化生长因子-β_1诱导的人胚肺成纤维细胞转分化及胶原合成 被引量:8

Prostaglandin E_2 inhibits transforming growth factor-β_1 triggered lung fibroblast-myofibroblast transdifferentiation and collagen Ⅰ production in vitro
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摘要 目的:研究前列腺素E2(PGE2)对转化生长因子-β1(TGF-β1)诱导人胚肺成纤维细胞(HLF)转分化及促胶原(COL)合成作用的干预。方法:HLF细胞生长至融合后分为①对照组、②TGF-β1组、③TGF-β1+PGE2组、④TGF-β1+吲哚美辛组,给予干预24h后用细胞免疫荧光及Westernblotting法观察发生转分化为肌成纤维细胞的标志蛋白α-平滑肌动蛋白(α-SMA)的表达,用RT-PCR法检测结缔组织生长因子(CTGF)mRNA和Ⅰ型胶原(COLⅠ)mRNA的水平,用免疫细胞化学法检测CTGF蛋白表达,比色法检测培养上清中羟脯氨酸含量。结果:TGF-β1可将HLF转分化为α-SMA阳性表达的肌成纤维细胞,PGE2则能抑制这种转分化作用;PGE2可显著减低TGF-β1致肌成纤维细胞、CTGFmRNA与蛋白水平(P<0.05)和COLⅠmRNA水平升高(P<0.05);吲哚美辛升高TGF-β1致HLF肌成纤维细胞CTGF与COLⅠ的表达;放线菌酮预处理肌成纤维细胞3h后再加入TGF-β1+PGE2,其COLⅠmRNA水平明显低于TGF-β1处理组水平(P<0.05)。结论:PGE2可抑制TGF-β1对成纤维细胞的转分化及促胶原合成作用,且可通过依赖CTGF和非依赖2种方式下调COLⅠ的转录。 AIM: To observe the effects of prostaglandin E2 on transforming growth factor-β1(TGF-β1)triggered human lung fetus fibroblast (HLF) transdifferentiation and connective tissue growth factor ( CTGF), collagen type I (COL I ) expression. METHODS: HLFs were treated with TGF - β1, the cells underwent phenotypic change to myofi- broblast. The marker of myofibroblast - α - smooth muscle actin (α - SMA) was detected by immunofluorescence. The α- SMA content was measured by Western blotting. The changes in CTGF and COL I at transcription levels were estimated by RT - PCR method. CTGF protein expression was evaluated by immunocytochemical. Cell culture medium hydroxyproline amount was measured by colormetric assay. RESULTS: PGE2 blocked TGF-β1 induced α -SMA positive myofibroblast transformation (P〈0.05). TGF-β1 induced CTGF mRNA expression. COL I mRNA level was decreased when co - in- cubated with PGE2 ( P 〈 0.05 ). Cycloheximide obviously elevated CTGF and COL I expression in myofibroblast. The COL I mRNA level in myofibroblast pretreated with cycloheximide was decreased when incubated with TGF -β1 and PGE2 compared with TGF -β1 treated group. CONCLUSION: PGE2 inhibits TGF - β1 induced transdifferentiation and collagen production, and reduces COL I expression through CTGF dependent and independent manners.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2008年第5期925-930,共6页 Chinese Journal of Pathophysiology
关键词 转化生长因子β 成纤维细胞 前列腺素E类 结缔组织生长因子 胶原I型 Transforming growth factor beta Fibroblasts Prostaglandins E Connective tissue growth factor Collagen type I
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参考文献13

  • 1Bonniaud P, Margetts P J, Ask K, et al. TGF - beta and Smad3 signaling link inflammation to chronic fibrogenesis [J]. J Immunol, 2005, 175(8):5390-5395.
  • 2Hodges R J, Jenkins RG, Wheeler CP, et al. Severity of lung injury in cyclooxygenase -2 -deficient mice is dependent on reduced prostaglandin E (2) production [ J ]. Am J Pathol, 2004, 165(5) :1663 - 1676.
  • 3Petkova DK, Clelland CA, Ronan JE, et al. Reduced expression of cyclooxygenase (COX) in idiopathic pulmonary fibrosis and sarcoidosis [ J ]. Histopathology, 2003, 43 (4) :381 -386.
  • 4Kelly M, Kolb M, Bonniaud P, et al. Re -evaluation of fibrogenic cytokines in lung fibrosis [ J ]. Curt Pharm Des, 2003, 9(1) :39 -40.
  • 5Yang X, Hou F, Taylor L,et al . Characterization of human cyclooxygenase 2 gene promotor localization of a TGF - β response element[ J]. Biochim Biophys Acta, 1997, 1350 ( 3 ) :287 - 292.
  • 6Pan LH, Yamauchi K, Uzuki M, et al. Type Ⅱ alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF [ J ]. Eur Respir J ,2001,17 (6) : 1220 - 1227.
  • 7张海燕,李幼姬,侯赛云,祝胜郎,余学清,孔耀中,叶任高.结缔组织生长因子在单侧输尿管梗阻大鼠肾组织中的表达[J].中国病理生理杂志,2006,22(3):427-430. 被引量:10
  • 8Grotendorst GR, Okochi H, Hagashi N, et al. A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene [J]. Cell Growth Differ,1996,7 (4) : 469 -473.
  • 9Jun Y, Gregory NP, Barbara S, et al. Role of prostaglandin E2 EP receptors and cAMP in the expression of connective tissue growth factor [ J ]. Arch Biochem Biophys, 2002,404(2) : 302 -330.
  • 10Gauldie J, Kolb M, Ask K, et al. Smad3 signaling involved in pulmonary fibrosis and emphysema [ J ]. Proc Am Thorac Soc, 2006, 3(8) :696 -702.

二级参考文献15

  • 1申洪.免疫组织化学染色定量方法研究(Ⅲ)[J].中国组织化学与细胞化学杂志,1995,4(1):89-92. 被引量:398
  • 2刘燕,樊均明.结缔组织生长因子在肾间质纤维化中的表达及其调控[J].中国病理生理杂志,2004,20(9):1725-1728. 被引量:1
  • 3Bradham DM,Igarashi A,Potter RL,et al.Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10[J].J Cell Biol,1991,114(2):1285-1294.
  • 4Kanemoto K,Usui J,Nitta K,et al.In situ expression of connective tissue growth factor in human crescentic glomerulonephritis[J].Virchows Arch,2004,444(3):257-263.
  • 5Gupta S,Clarkson MR,Duggan J,et al.Connective growth factor:potential role in glomerulosclerosis and tubulointerstitial fibrosis[J].Kidney Int,2000,58(5):1389-1399.
  • 6Hyer EG,Shegogue D,Markiewicz M,et al.TGF-β and CTGF have overlapping and distinct fibrogenic effects on human renal cells[J].Am J Physiol Renal Physiol,2002,45(3):F707-F716.
  • 7Solez K,Axelsen RA,Benediktsson H,et al.International standardization of criteria for the histologic diagnosis of renal allograft rejection:the Banff working classification of kidney transplant pathology[J].Kidney Int,1993,44(8):411-422.
  • 8Roberts IS,Burrows C,Shanxs JH,et al.Interstitial myofibroblasts:Predictors of progression in membranous nephropathy[J].J Clin Pathol,1997,50(7):123-127.
  • 9Ito Y,Aten J,Bende RJ,et al.Expression of connective tissue growth factor in human renal fibrosis [J].Kidney Int,1998,53(4):853-861.
  • 10Ihn H.Pathogenesis of fibrosis:role of TGF-beta and CTGF [J].Curr Opin Rheumatol,2002,14(6):681-685.

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