Release of biologically active TGF-β1 by alveolar epithelial cells results in pulmonary fibrosis
Release of biologically active TGF-β1 by alveolar epithelial cells results in pulmonary fibrosis
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DOI：
10.1152/ajplung.00298.2002
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发表时间：
2003-09-01
影响因子：
4.9
通讯作者：
Khalil, N
中科院分区：
文献类型：
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作者：
Xu, YD;Hua, JS;Khalil, N
特发性肺纤维化（IPF）是一种进行性致死性肺纤维化疾病。转化生长因子（TGF）-β 1以生物活性构象存在于晚期IPF病变衬里上皮细胞中。为了确定肺泡上皮细胞（AEC）的生物活性TGF-β 1的异常表达的作用，使用逆转录病毒pMX-Ls 223，225-TGF-β 1用TGF-β 1基因转染正常大鼠肺的AEC。使用地高辛标记的pMX中所含嘌呤霉素抗性基因的cDNA进行原位杂交，证明pMX-L-s233，225-TGF-β 1被选择性地转染到外植体的AEC中。在用pMX-L-s223，225-TGF-β 1处理后7天获得的覆盖外植体的条件培养基含有14.5 +/-3.15 pg/ml的活性TGF-β 1。通过使用转染后14天获得的外植体切片的Masson三色染色，存在与IPF中的病变相似的病变，其特征在于II型AEC增生、间质增厚、间质和上皮下胶原广泛增加、成纤维细胞数量增加以及类似成纤维细胞芽的区域。在用pMX-L-s223、225-TGF-β 1处理的外植体中，胶原蛋白I、III、IV和V以及纤连蛋白增加。当前研究的结果表明，IPF可能是一种上皮细胞而非炎性细胞疾病。
Idiopathic pulmonary fibrosis (IPF) is a progressive fatal fibrotic lung disease. Transforming growth factor (TGF)-beta1 is present in a biologically active conformation in the epithelial cells lining lesions with advanced IPF. To determine the role of aberrant expression of biologically active TGF-beta1 by alveolar epithelial cells (AECs), the AECs of explanted normal rat lungs were transfected with the TGF-beta1 gene using the retrovirus pMX-Ls223,225-TGF-beta1. In situ hybridization using a digoxigenin-labeled cDNA of the puromycin resistance gene contained in the pMX demonstrated that pMX-L-s233,225-TGF-beta1 was selectively transfected into AECs of the explants. Conditioned media overlying explants obtained 7 days after being treated with pMX-L-s223,225-TGF-beta1 contained 14.5 +/- 3.15 pg/ml of active TGF-beta1. With the use of Masson's trichrome staining of explant sections obtained 14 days after transfection, there were lesions similar to those in IPF, characterized by type II AEC hyperplasia, interstitial thickening, extensive increase in interstitial and subepithelial collagen, an increase in the number of fibroblasts, and areas resembling fibroblast buds. Collagens I, III, IV, and V and fibronectin were increased in explants treated with pMX-L-s223,225-TGF-beta1. The findings in the current study suggest that IPF may be a disorder of epithelial cells and not inflammatory cells.