Department of Basic Medicine, Haihe Clinical College of Tianjin Medical University, Tianjin 300350, P.R. China.
Department of Respiratory Medicine, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8155-8163. doi: 10.3892/mmr.2017.7636. Epub 2017 Sep 26.
The interaction between airway epithelial progenitor cells and their microenvironment is critical for maintaining lung homeostasis. This microenvironment includes fibroblast cells, which support the growth of airway progenitor cells. However, the mechanism of this support is not fully understood. In the present study, the authors observed that inhibition of transforming growth factor (TGF)‑β signal with SB431542 promotes the expression of hepatocyte growth factor (HGF) in fibroblast cells. The HGF receptor, c‑Met, is expressed on airway progenitor cells; HGF promotes the colony‑forming ability of airway progenitor cells. The deletion of Smad4 in airway progenitor cells increases the colony‑forming ability, suggesting that Smad4 plays a negative role in the regulating the proliferation of airway progenitor cells. These data demonstrated that the regulation of airway progenitor cells by TGF‑β depends on TGF‑βR1/2 on stromal cells, rather than on epithelial progenitor cells. These data suggested a role for the TGF‑β‑TGF‑βR1/2‑HGF‑Smad4 axis in airway epithelial homeostasis and sheds new light on the interaction between airway progenitor cells and their microenvironment.
气道上皮祖细胞与其微环境之间的相互作用对于维持肺内稳态至关重要。该微环境包括成纤维细胞，其支持气道祖细胞的生长。然而，这种支持的机制尚不完全清楚。在本研究中，作者观察到用 SB431542 抑制转化生长因子 (TGF)-β 信号可促进成纤维细胞中肝细胞生长因子 (HGF)的表达。HGF 受体 c-Met 在气道祖细胞上表达；HGF 可促进气道祖细胞的集落形成能力。气道祖细胞中 Smad4 的缺失增加了集落形成能力，表明 Smad4 在调节气道祖细胞增殖方面发挥负调控作用。这些数据表明，TGF-β 对气道祖细胞的调节依赖于基质细胞上的 TGF-βR1/2，而不是上皮祖细胞。这些数据表明 TGF-β-TGF-βR1/2-HGF-Smad4 轴在气道上皮稳态中起作用，并为气道祖细胞与其微环境之间的相互作用提供了新的视角。
