Thorac Cardiovasc Surg 2013; 61(08): 747-753
DOI: 10.1055/s-0032-1331574
Original Basic Science
Georg Thieme Verlag KG Stuttgart · New York

Expression of Transforming Growth Factor Beta 1 in Lung Tissue during Cardiopulmonary Bypass-Induced Lung Injury in Dogs

Xiaofei Wang
1   Department of Anesthesiology, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, P.R. China
,
Xianfeng Qu
1   Department of Anesthesiology, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, P.R. China
,
Qiaosheng Zhong
1   Department of Anesthesiology, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, P.R. China
,
Qianyu Li
1   Department of Anesthesiology, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, P.R. China
,
Dongguo Wang
2   Clinical Laboratory, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, P.R. China
› Author Affiliations
Further Information

Publication History

18 July 2012

21 September 2012

Publication Date:
06 December 2012 (online)

Abstract

Background Cardiopulmonary bypass (CPB) is a necessary technique for cardiac surgery and usually induces acute lung injury. Transforming growth factor β1 (TGFβ1) has been found to play a crucial role in the pathogenesis of inflammatory diseases; however, whether TGFβ1 is also involved in CPB-induced lung injury has yet to be determined. Therefore, we aimed to investigate the TGFβ1 expression in the lungs of dogs after CPB.

Methods A total of 36 healthy mongrel dogs were randomly assigned to control and CPB groups. Six dogs in each group were killed before, 30 min after the operation, and 60 min after the operation (T0, T1, and T2). Lung injury was evaluated by hematoxylin and eosin staining. Respiratory index (RI), oxygenation index (OI), malondialdehyde (MDA) content in the lung, and pulmonary permeability index (PPI) were determined at each time point. TGFβ1 expression was determined using real-time reverse transcription polymerase chain reaction and immunohistochemistry.

Results There was a serious lung injury observed after CPB in dogs. RI increased and OI decreased in the dogs after CPB. The MDA content significantly increased after CPB; however, no significant change of MDA occurred in the control group. A significant increase of PPI was detected in CPB group at the T1 and T2 time points compared with that at the T0 time point. TGFβ1 expression in the lung was increased after CPB on both the mRNA and protein levels. Positive correlations between TGFβ1 mRNA level and MDA (r = 0.867, p < 0.01) and between TGFβ1 mRNA and PPI (r = 0.821, p < 0.01) were detected by linear correlation.

Conclusion The upregulation of TGFβ1 expression plays an important role in the development and progression of CPB-induced acute lung injury.

 
  • References

  • 1 Asimakopoulos G, Smith PL, Ratnatunga CP, Taylor KM. Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass. Ann Thorac Surg 1999; 68 (3) 1107-1115
  • 2 Canet J, Gallart L, Gomar C , et al; ARISCAT Group. Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology 2010; 113 (6) 1338-1350
  • 3 Park S, Ahn JY, Lim MJ , et al. IM-412 inhibits transforming growth factor beta-induced fibroblast differentiation in human lung fibroblast cells. Biochem Biophys Res Commun 2010; 399 (2) 268-273
  • 4 Miyake T, Alli NS, McDermott JC. Nuclear function of Smad7 promotes myogenesis. Mol Cell Biol 2010; 30 (3) 722-735
  • 5 Mishra L, Derynck R, Mishra B. Transforming growth factor-beta signaling in stem cells and cancer. Science 2005; 310 (5745) 68-71
  • 6 Wipff PJ, Hinz B. Integrins and the activation of latent transforming growth factor beta1 - an intimate relationship. Eur J Cell Biol 2008; 87 (8-9) 601-615
  • 7 Ghafoori P, Yoshimura T, Turpie B, Masli S. Increased IkappaB alpha expression is essential for the tolerogenic property of TGF-beta-exposed APCs. FASEB J 2009; 23 (7) 2226-2234
  • 8 Lan HY. Smad7 as a therapeutic agent for chronic kidney diseases. Front Biosci 2008; 13: 4984-4992
  • 9 Xiao YQ, Freire-de-Lima CG, Janssen WJ , et al. Oxidants selectively reverse TGF-beta suppression of proinflammatory mediator production. J Immunol 2006; 176 (2) 1209-1217
  • 10 Cho ML, Min SY, Chang SH , et al. Transforming growth factor beta 1(TGF-beta1) down-regulates TNFalpha-induced RANTES production in rheumatoid synovial fibroblasts through NF-kappaB-mediated transcriptional repression. Immunol Lett 2006; 105 (2) 159-166
  • 11 Kulkarni AB, Ward JM, Yaswen L , et al. Transforming growth factor-beta 1 null mice. An animal model for inflammatory disorders. Am J Pathol 1995; 146 (1) 264-275
  • 12 Boivin GP, O'Toole BA, Orsmby IE , et al. Onset and progression of pathological lesions in transforming growth factor-beta 1-deficient mice. Am J Pathol 1995; 146 (1) 276-288
  • 13 Meng XM, Huang XR, Xiao J , et al. Diverse roles of TGF-β receptor II in renal fibrosis and inflammation in vivo and in vitro. J Pathol 2012; 227 (2) 175-188
  • 14 Wang W, Koka V, Lan HY. Transforming growth factor-beta and Smad signalling in kidney diseases. Nephrology (Carlton) 2005; 10 (1) 48-56
  • 15 Inazaki K, Kanamaru Y, Kojima Y , et al. Smad3 deficiency attenuates renal fibrosis, inflammation,and apoptosis after unilateral ureteral obstruction. Kidney Int 2004; 66 (2) 597-604
  • 16 Huang XR, Chung AC, Yang F , et al. Smad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodeling. Hypertension 2010; 55 (5) 1165-1171
  • 17 Huang XR, Chung AC, Zhou L, Wang XJ, Lan HY. Latent TGF-beta1 protects against crescentic glomerulonephritis. J Am Soc Nephrol 2008; 19 (2) 233-242
  • 18 Broekelmann TJ, Limper AH, Colby TV, McDonald JA. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci U S A 1991; 88 (15) 6642-6646
  • 19 Wesselkamper SC, Case LM, Henning LN , et al. Gene expression changes during the development of acute lung injury: role of transforming growth factor beta. Am J Respir Crit Care Med 2005; 172 (11) 1399-1411
  • 20 Kaminski N, Allard JD, Pittet JF , et al. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proc Natl Acad Sci U S A 2000; 97 (4) 1778-1783
  • 21 Hurst V IV, Goldberg PL, Minnear FL, Heimark RL, Vincent PA. Rearrangement of adherens junctions by transforming growth factor-beta1: role of contraction. Am J Physiol 1999; 276 (4 Pt 1) L582-L595
  • 22 Pittet JF, Griffiths MJ, Geiser T , et al. TGF-beta is a critical mediator of acute lung injury. J Clin Invest 2001; 107 (12) 1537-1544
  • 23 Frank J, Roux J, Kawakatsu H , et al. Transforming growth factor-beta1 decreases expression of the epithelial sodium channel alphaENaC and alveolar epithelial vectorial sodium and fluid transport via an ERK1/2-dependent mechanism. J Biol Chem 2003; 278 (45) 43939-43950
  • 24 Willis BC, Kim KJ, Li X, Liebler J, Crandall ED, Borok Z. Modulation of ion conductance and active transport by TGF-beta 1 in alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol 2003; 285 (6) L1192-L1200
  • 25 Williams EA, Welty SE, Geske RS , et al. Liquid lung ventilation reduces neutrophil sequestration in a neonatal swine model of cardiopulmonary bypass. Crit Care Med 2001; 29 (4) 789-795
  • 26 Mao ZM, Song HY, Yang LL , et al. [Effects of the mixture of Swertia pseudochinensis Hara and Silybum marianum Gaertn extracts on CCl(4)-induced liver injury in rats with non-alcoholic fatty liver disease]. Zhong Xi Yi Jie He Xue Bao 2012; 10 (2) 193-199
  • 27 Takao Y, Mikawa K, Nishina K, Obara H. Attenuation of acute lung injury with propofol in endotoxemia. Anesth Analg 2005; 100 (3) 810-816 table of contents.
  • 28 Giri SN, Hyde DM, Hollinger MA. Effect of antibody to transforming growth factor beta on bleomycin induced accumulation of lung collagen in mice. Thorax 1993; 48 (10) 959-966
  • 29 Kwong KY, Literat A, Zhu NL , et al. Expression of transforming growth factor beta (TGF-beta1) in human epithelial alveolar cells: a pro-inflammatory mediator independent pathway. Life Sci 2004; 74 (24) 2941-2957
  • 30 Jardine H, MacNee W, Donaldson K, Rahman I. Molecular mechanism of transforming growth factor (TGF)-beta1-induced glutathione depletion in alveolar epithelial cells. Involvement of AP-1/ARE and Fra-1. J Biol Chem 2002; 277 (24) 21158-21166
  • 31 Manabe E, Handa O, Naito Y , et al. Astaxanthin protects mesangial cells from hyperglycemia-induced oxidative signaling. J Cell Biochem 2008; 103 (6) 1925-1937
  • 32 Itagaki T, Shimizu I, Cheng X , et al. Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells. Gut 2005; 54 (12) 1782-1789