Basic & Clinical Medicine ›› 2008, Vol. 28 ›› Issue (3): 232-237.

• 研究论文 • Previous Articles     Next Articles

Role of transforming growth factor-?1 tnducing myofibroblast formation in hypoxic pulmonary vascular remodeling

Bo-wan LI, Yong-liang JIANG, Ai-guo DAI   

  1. Department of Respiratory Internal Medicine; the Third Affiliated Hospital of Nanhua University
  • Received:2007-05-08 Revised:2007-08-31 Online:2008-03-25 Published:2008-03-25
  • Contact: Yong-liang JIANG,

Abstract: Objective To investigate transforming growth factor-┈1(TGF-┈1) induces myofibroblast formation in hypoxic pulmonary vascular remodeling of rats. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21days. Mean pulmonary arterial pressure (mPAP), vessel morphometry, right ventricle hypertrophy index (RVHI) were measured. Immunocytochemistry were used to measure the expression of メ-smooth-muscle actin(メ-SMA) and TGF-┈1 in pulmonary artery walls, however, in situ hybridization were used to measure the expression of TGF-┈1 mRNA in pulmonary artery walls. Ultrastructural characteristics of cell phenotype in alveolar wall vessels were observed by electron microscopy. Cell culture observed human embryonic lung fibroblasts(KMB17) phenotype after induction of hypoxia and TGF-┈1. Results (1) mPAP increased significantly after 7-day of hypoxia[(18.41【0.37)mmHg,P<0.05]. Pulmonary artery remodeling index and right ventricle hypertrophy became evident after 14-day of hypoxia. (2) The distribution of nonmuscular, partially muscular, and muscular vessels(39%、46%、15% ) is significantly different (PX2<0.005= from hypoxia 7d than that in the control group (60%、35%、5% ).(3)The intra-acinar pulmonary arteries with cells expressing メ-SMA increased most with hypoxic time by immunocytochemistry. TGF-┈1 mRNA expression in pulmonary arterial walls was increased significantly after 14 days of hypoxia(0.385【0.028, P<0.01),but showed no obvious changes after 3 or 7 days of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-┈1 staining was poorly positive in control rats, but was markedly enhanced after 3 days of hypoxia(0.198【0.031,P<0.01), reaching its peak after 7 days of hypoxia(0.267【0.035,P<0.01). (4) The myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments and a well-developed rough endoplasmic reticulum.(5) Cell culture showed that hypoxia induced KMB17 phenotype transforming and TGF-モ1 accelerated its transforming.Conclusion It is reasonable to believe that transforming growth factor-┈1(TGF-┈1) induces myofibroblast formation are the important causes in hypoxic pulmonary vascular remodeling of rats.