Department of Emergency, Shengjing Hospital of China Medical University, Shenyang, China.
Front Biosci (Landmark Ed). 2012 Jun 1;17(7):2667-74. doi: 10.2741/4077.
Pulmonary fibrosis, defined as the accumulation of connective tissue in the lungs, is a severe and often fatal form of interstitial lung disease. Transforming growth factor-beta (TGF-beta) is a powerful activator of connective tissue synthesis and fibroblast proliferation in the lung, and a critical paracrine signal for the development of pulmonary fibrosis. To investigate signaling pathways downstream of TGF- beta that contribute to lung fibrosis, TGF- beta stimulation of fibroblasts was replicated by treating NIH3T3 fibroblasts with conditioned medium (CM) from TGF- beta -treated type II alveolar epithelial cells (ATII cells). The data showed that fibroblast growth factor 2 (FGF-2) signaling is responsible for TGF-beta 1 CM-induced fibroblast proliferation, while it does not affect TGF-beta 1 CM-induced fibrotic differentiation. Moreover, fibroblast proliferation and differentiation induced by TGF- beta CM was totally abrogated by pretreatment of NIH3T3 cells with the specific ERK1/2 inhibitor, PD98059. These findings indicate that FGF-2 secreted by alveolar epithelial cells in response to TGF- beta 1 induces fibroblast proliferation and fibrotic activation through the ERK kinase pathway.
肺纤维化定义为肺部结缔组织的积累，是一种严重且常常致命的间质性肺疾病形式。转化生长因子-β（TGF-β）是肺中结缔组织合成和成纤维细胞增殖的强大激活剂，也是肺纤维化发生的关键旁分泌信号。为了研究促进肺纤维化的 TGF-β下游信号通路，用 TGF-β处理的 II 型肺泡上皮细胞（ATII 细胞）的条件培养基（CM）处理 NIH3T3 成纤维细胞，复制 TGF-β对成纤维细胞的刺激。结果表明，成纤维细胞生长因子 2（FGF-2）信号负责 TGF-β1 CM 诱导的成纤维细胞增殖，而不影响 TGF-β1 CM 诱导的纤维分化。此外，用 ERK1/2 特异性抑制剂 PD98059 预处理 NIH3T3 细胞可完全阻断 TGF-β CM 诱导的成纤维细胞增殖和分化。这些发现表明，肺泡上皮细胞对 TGF-β1 的反应分泌的 FGF-2 通过 ERK 激酶途径诱导成纤维细胞增殖和纤维激活。
