In vivo mitogenic action of HGF on lung epithelial cells: Pulmotrophic role in lung regeneration
In vivo mitogenic action of HGF on lung epithelial cells: Pulmotrophic role in lung regeneration
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DOI：
10.1152/ajplung.1996.270.6.l1031
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发表时间：
1996-06-01
影响因子：
4.9
通讯作者：
Nakamura, T
中科院分区：
文献类型：
--
作者：
Ohmichi, H;Matsumoto, K;Nakamura, T
肝细胞生长因子（HGF）对上皮细胞具有有丝分裂、形态发生和动原活性，在肝脏和肾脏的再生中起重要作用。我们前期研究发现，实验动物急性肺损伤后，肺内快速诱导HGF基因表达，肺部疾病患者血液中HGF水平升高。为了寻找HGF在肺再生中的可能的肺营养功能，我们在体外检测了HGF对气管上皮细胞的有丝分裂活性，并评估了HGF对小鼠急性肺损伤后肺再生的影响。HGF对原代培养大鼠气管上皮细胞增殖和DNA合成具有剂量依赖性。人重组HGF （10 μ g）静脉注射。鼠标(1)。经气管内灌注10 mM HCl诱导的急性肺损伤小鼠，其气道上皮细胞的DNA合成水平比未注射hgf的小鼠高3倍，但对肺泡上皮细胞的DNA合成没有刺激作用。然而，高剂量注射hgf (100 μ g)，鼠标(1)。day(-1))刺激肺泡上皮细胞的DNA合成。这些结果表明，在体内和体外，HGF是气道上皮细胞和肺泡上皮细胞的有效丝裂原。急性肺损伤后肺再生过程中，HGF可能作为肺营养因子参与气道和肺泡再生。
Hepatocyte growth factor (HGF) has mitogenic, morphogenic, and motogenic activities on epithelial cells and plays important roles in regeneration of the liver and the kidney. We previously found that the expression of HGF gene is rapidly induced in the lung after acute lung injury in experimental animals and that HGF levels are elevated in blood of patients with lung diseases. To search for a possible pulmotrophic function of HGF in lung regeneration, we examined the mitogenic activity of HGF on tracheal epithelial cells in vitro and evaluated the efficacy of HGF-administration on lung regeneration after acute lung injury in mice. HGF markedly stimulated proliferation and DNA synthesis of rat tracheal epithelial cells in primary culture in a dose-dependent manner. The intravenous injection of human recombinant HGF (10 mu g . mouse(-1). day(-1)) into mice with acute lung injury induced by the intratracheal infusion of 10 mM HCl stimulated DNA synthesis of airway epithelial cells to levels threefold higher than those in mice with no HGF-injections, but it did not stimulate DNA synthesis of alveolar epithelial cells. However, HGF-injection at higher dose (100 mu g . mouse(-1). day(-1)) stimulated DNA synthesis of alveolar epithelial cells in vivo. These results indicate that HGF is a potent mitogen for airway epithelial cells and alveolar epithelial cells in vivo as well as in vitro. HGF may act as pulmotrophic factor responsible for airway and alveolar regeneration during lung regeneration after acute lung injury.