EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR RECEPTOR IS INCREASED FOLLOWING BLEOMYCIN-INDUCED LUNG INJURY IN RATS
EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR RECEPTOR IS INCREASED FOLLOWING BLEOMYCIN-INDUCED LUNG INJURY IN RATS
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DOI：
10.1165/ajrcmb.11.5.7524566
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发表时间：
1994-11-01
影响因子：
6.4
通讯作者：
CLARK, JG
中科院分区：
文献类型：
--
作者：
MADTES, DK;BUSBY, HK;CLARK, JG
为了研究转化生长因子-cy (TGF-cr) 和表皮生长因子受体 (EGF-R) 在急性肺损伤纤维增殖反应中的潜在作用，我们测定了博来霉素损伤和对照大鼠肺的肺稳态 TGF-α 和 EGF-R mRNA 水平、TGF-α 蛋白水平以及 TGF-cu 和 EGFR 免疫反应蛋白的分布。单次气管内注射博莱霉素后第 2 天和第 4 天，TGF-α mRNA 水平分别增加至对照值的 159% 和 184%。博莱霉素滴注后第 1、7 和 14 天，EGF-R mRNA 水平分别增加至对照值的 163%、314% 和 170%。博莱霉素给药后 4 天，全肺提取物中的 TGF-α 蛋白水平增加至对照值的 230%。在对照和博来霉素损伤的动物的巨噬细胞、肺泡间隔细胞和气道上皮中检测到TGF-α和EGF-R免疫反应性，肺损伤后特异性免疫染色细胞的强度和数量明显增加。在细胞增殖灶和肺泡内纤维化区域检测到 TGF-α 和 EGF-R 免疫反应蛋白。我们得出结论，TGF-α和EGF-R存在于正常和博来霉素损伤的大鼠肺中，并且这种生长因子及其受体的表达在肺损伤后上调。这些结果表明，TGF-α和EGFR表达的增加可能是调节急性肺损伤的纤维增殖反应的重要机制。
To investigate the potential role of transforming growth factor-cy (TGF-cr) and the epidermal growth factor receptor (EGF-R) in the fibroproliferative response to acute lung injury, we determined lung steady-state TGF-alpha and EGF-R mRNA levels, TGF-alpha protein levels, and the distribution of TGF-cu and EGFR immunoreactive protein of bleomycin-injured and control rat lungs. At 2 and 4 days after a single intratracheal injection of bleomycin, TGF-alpha mRNA levels increased to 159% and 184% of control values, respectively. EGF-R mRNA levels increased to 163%, 314%, and 170% of control values at 1, 7, and 14 days after bleomycin instillation. TGF-alpha protein levels in whole lung extracts increased to 230% of control values at 4 days after bleomycin administration. TGF-alpha and EGF-R immunoreactivity was detected in macrophages, alveolar septal cells, and airway epithelium of control and bleomycin-injured animals with an apparent increase in the intensity and number of specifically immunostained cells following lung injury. TGF-alpha and EGF-R immunoreactive proteins were detected in foci of cellular proliferation and in areas of intraalveolar fibrosis. We conclude that TGF-alpha and the EGF-R are present in normal and bleomycin-injured rat lung and that the expression of this growth factor and its receptor are up-regulated following lung injury. These results suggest that increased expression of TGF-alpha and the EGFR may be an important mechanism that modulates the fibroproliferative response to acute lung injury.