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首页> 外文期刊>American Journal of Physiology >Changes in Smad expression and subcellular localization in bleomycin-induced pulmonary fibrosis.
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Changes in Smad expression and subcellular localization in bleomycin-induced pulmonary fibrosis.

机译：博莱霉素诱导的肺纤维化中Smad表达和亚细胞定位的变化。

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摘要

Administration of bleomycin (BM) produces inflammation and fibrosis of the lung in humans and experimental animals. The molecular defects by which BM induces these pathological effects have not been studied in detail. We studied the expression of Smad family proteins, key molecules involved in mediating transforming growth factor (TGF)-beta signaling from the cell membrane to the nucleus, during the early and late phases of BM-induced fibrogenesis. Pulmonary fibrosis was induced in male Sprague-Dawley rats by a single intratracheal injection (1.5 units) of BM. Control rats received saline. Rats were killed at 3, 5, 7, 14, and 28 days after BM, cytosolic and nuclear proteins were extracted and isolated from lung tissues, and Smad proteins were probed with specific antibodies. In BM-exposed lung tissue, compared with control, Smad3 decreased persistently in the cytosol and increased transiently in the nucleus. There was a persistent increase in phosphorylation and nuclear accumulation of Smad2/3. Smad4 was increased transiently in both the cytosol and nucleus. A significant and progressive decrease in the expression of Smad7, the endogenous inhibitor of TGF-beta/Smad signaling, was observed after BM instillation. Collectively, our results indicate that an imbalance between agonistic Smads2-4 and antagonistic Smad7 may result in the unchecked activation of an autocrine TGF-beta loop, which contributes to the pathogenesis of BM-induced pulmonary fibrosis.
机译：介绍博来霉素（BM）在人类和实验动物中产生肺的炎症和纤维化。 BM诱导这些病理效应的分子缺陷尚未详细研究。我们研究了Smad家族蛋白的表达，在BM诱导的纤维发生的早期和晚期阶段期间，在细胞膜中介导转化生长因子（TGF）-Beta信号传导的关键分子。通过单一的腹腔内注射（1.5单位）的BM，在雄性Sprague-Dawley大鼠中诱导肺纤维化。对照大鼠接受盐水。大鼠在3,5,7,14和28天杀死BM后28天，从肺组织中提取并分离胞质和核蛋白，并用特异性抗体探测Smad蛋白。在BM暴露的肺组织中，与对照相比，Smad3在细胞溶溶胶中持续下降并在细胞核中瞬时增加。 Smad2 / 3的磷酸化和核积累存在持续增加。 Smad4在细胞溶胶和细胞核中瞬时增加。在BM灌注后观察到Smad7，TGF-β/ Smad信号传导的内源抑制剂的表达的显着和逐渐降低。集体，我们的结果表明，激酶Smads2-4和拮抗Smad7之间的不平衡可能导致自分泌TGF-β环的未经检查的激活，这有助于BM诱导的肺纤维化的发病机制。

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