TRANSFORMING GROWTH FACTOR-BETA-1 IS PRESENT AT SITES OF EXTRACELLULAR-MATRIX GENE-EXPRESSION IN HUMAN PULMONARY FIBROSIS
TRANSFORMING GROWTH FACTOR-BETA-1 IS PRESENT AT SITES OF EXTRACELLULAR-MATRIX GENE-EXPRESSION IN HUMAN PULMONARY FIBROSIS
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DOI：
10.1073/pnas.88.15.6642
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发表时间：
1991-08-01
影响因子：
11.1
通讯作者：
MCDONALD, JA
中科院分区：
文献类型：
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作者：
BROEKELMANN, TJ;LIMPER, AH;MCDONALD, JA
特发性肺纤维化是一种不可避免的致命疾病，其特征是终末空气间隙内结缔组织沉积，导致肺功能丧失和最终呼吸衰竭。先前，我们证明了表达高水平纤维连接蛋白、前胶原蛋白和平滑肌肌动蛋白的活化成纤维细胞灶与愈合伤口中发现的相似，是特发性肺纤维化结缔组织沉积和瘢痕形成的原因。利用原位杂交和免疫组织化学，我们现在证明了转化生长因子- β -1 （tgf - β -1）的存在，这是一种有效的促纤维化细胞因子，在含有这些活化的成纤维细胞的病灶中。这些结果表明，基质相关的tgf - β -1可能作为结缔组织基因持续表达的刺激。tgf - β -1的一个潜在来源是肺泡巨噬细胞，我们证实特发性肺纤维化患者肺组织的肺泡巨噬细胞中大量表达tgf - β -1 mRNA。
Idiopathic pulmonary fibrosis is an inexorably fatal disorder characterized by connective tissue deposition within the terminal air spaces resulting in loss of lung function and eventual respiratory failure. Previously, we demonstrated that foci of activated fibroblasts expressing high levels of fibronectin, procollagen, and smooth muscle actin and thus resembling those found in healing wounds are responsible for the connective tissue deposition and scarring in idiopathic pulmonary fibrosis. Using in situ hybridization and immunohistochemistry, we now demonstrate the presence of transforming growth factor-beta-1 (TGF-beta-1), a potent profibrotic cytokine, in the foci containing these activated fibroblasts. These results suggest that matrix-associated TGF-beta-1 may serve as a stimulus for the persistent expression of connective tissue genes. One potential source of the TGF-beta-1 is the alveolar macrophage, and we demonstrate the expression of abundant TGF-beta-1 mRNA in alveolar macrophages in lung tissue from patients with idiopathic pulmonary fibrosis.