Mori Masahide, Morishita Hiroshi, Nakamura Hideji, Matsuoka Hiroto, Yoshida Kenya, Kishima Yoshihiko, Zhou Zhiwei, Kida Hiroshi, Funakoshi Toshiki, Goya Sho, Yoshida Mitsuhiro, Kumagai Toru, Tachibana Isao, Yamamoto Yoichi, Kawase Ichiro, Hayashi Seiji
Department of Molecular Medicine, Osaka University Graduate University Graduate School of Medicine, Osaka, Japan.
Am J Respir Cell Mol Biol. 2004 Apr;30(4):459-69. doi: 10.1165/rcmb.2003-0013OC. Epub 2003 Sep 11.
Lung epithelial cells have an integral role in the maintenance of lung homeostasis; however, the regulatory mechanism thereof has not been fully clarified. Recently, hepatoma-derived growth factor (HDGF) was reported to be involved in organ development and remodeling through its mitogenic effect. We investigated the biological role of HDGF in lung remodeling. HDGF was more highly expressed in the lungs of idiopathic pulmonary fibrosis, chiefly in the epithelial cells, than in control nonfibrotic lungs. We also confirmed the expression of HDGF protein and mRNA in the lungs of bleomycin-instilled mice, mainly in the bronchial and alveolar epithelial cells, by immunohistochemical analysis and in situ hybridization. We found that recombinant HDGF promoted DNA synthesis in rat alveolar epithelial cells and A549 cells in vitro. Endogenous HDGF overexpressed by gene transfer was translocated into the nucleus and promoted the proliferation of A549 cells. In vivo intratracheal instillation of recombinant HDGF induced the proliferation of bronchial and alveolar epithelial cells without causing marked interstitial inflammation. These findings suggest that HDGF may be involved in lung remodeling after injury by promoting the proliferation of lung epithelial cells, probably in an autocrine manner.
肺上皮细胞在维持肺内环境稳定中发挥着不可或缺的作用；然而，其调控机制尚未完全阐明。最近，有报道称肝癌衍生生长因子（HDGF）通过其促有丝分裂作用参与器官发育和重塑。我们研究了HDGF在肺重塑中的生物学作用。与对照非纤维化肺相比，HDGF在特发性肺纤维化患者的肺中表达更高，主要在上皮细胞中。通过免疫组织化学分析和原位杂交，我们还证实了博来霉素诱导小鼠肺中HDGF蛋白和mRNA的表达，主要在支气管和肺泡上皮细胞中。我们发现重组HDGF在体外促进大鼠肺泡上皮细胞和A549细胞的DNA合成。通过基因转移过表达的内源性HDGF易位至细胞核并促进A549细胞的增殖。体内气管内滴注重组HDGF可诱导支气管和肺泡上皮细胞增殖，而不会引起明显的间质炎症。这些发现表明，HDGF可能通过促进肺上皮细胞增殖，可能以自分泌方式参与损伤后的肺重塑。
