Role of insulin like growth factor axis in the bleomycin induced lung injury in rats
Role of insulin like growth factor axis in the bleomycin induced lung injury in rats
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DOI：
10.1016/j.yexmp.2017.01.004
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发表时间：
2017-02-01
影响因子：
3.6
通讯作者：
Ravi, Krishnan
中科院分区：
文献类型：
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作者：
Kotarkonda, Lakshmi Kanth;Kulshrestha, Ritu;Ravi, Krishnan
背景：肺泡上皮细胞损伤已被认为是肺纤维化发生和进展的致病因素。然而，11 型肺泡上皮细胞 (AEC) 在上皮间质转化 (EMT) 中的作用尚存在争议。 目的：本研究在注射博来霉素的大鼠中进行，研究了 a) II 型 AEC 中胰岛素生长因子 (IGF-1)、胰岛素生长因子结合蛋白 5 (IGFBP-5) 和转化生长因子 (TGF-β 1) 的表达，b) II 型 AEC 在上皮间质转化 (EMT) 中的作用。 EMT 和细胞外基质 (ECM) 形成，以及 c) 吡格列酮对所有上述参数的影响。方法：将雄性 Wistar 大鼠分为三组：I 组（盐水对照）、II 组（博来霉素，单次气管内滴注，7 U/kg）和 III 组（博来霉素 + 吡格列酮（口服 40 mg/kg/天，在博来霉素滴注后 7 天开始，如组中那样） II). IGF-1、IGFBP-5、TGF-β1、表面活性蛋白 C（SP-C，作为 II 型 AEC 的标志物）和 α-平滑肌肌动蛋白（α-SMA，作为 EMT 的标志物）的蛋白表达在第 7 天（第 1 组和第 II 组）以及第 14、21 和 35 天（所有三组）进行测定。结果：IGFBP-5 和 IGF-1 表达显着降低。与第 7 天到第 35 天相比，第 II 组的 II 型 AEC 中的 TGF-β 1 表达显着增加。从第 7 天到第 35 天，在进行 EMT 的 II 型 AEC 中观察到 SP-C 和 a-SMA 表达的增加及其共定位。在使用吡格列酮的第 III 组中，也观察到 ECM 的伴随重塑和沉积。 II型AECs中IGFBP-5和IGF-1表达以及TGF-β1下调，肺组织实性面积分数、EMT和ECM显着降低。结论：II型AECs中IGFBP-5、IGF-1和TGF-β1在博来霉素引起的肺损伤中起关键作用，吡格列酮通过恢复IGFBP-5和IGFBP-5和TGF-β1的表达来减轻肺损伤/纤维化。 II 型 AEC 中 IGF-1 和减少 TGF-β 1 表达 (C) 2016 年由 Elsevier Inc. 出版。
Background: Alveolar epithelial cell injury has been proposed as a causative factor for the onset and progression of pulmonary fibrosis. However, the role of type 11 alveolar epithelial cells (AECs) in the epithelial mesenchymal transition (EMT) is controversial.Aims: The present study performed in rats instilled with bleomycin investigated a) the expressions of the insulin growth factor (IGF-1) and insulin growth factor binding protein 5 (IGFBP-5) and transforming growth factor (TGF-beta 1) in the type II AECs, b) the role of type II AECs in EMT and extracellular matrix (ECM) formation and, c) the effect of pioglitazone on all the above parameters.Methods: Male Wistar rats were divided into three Groups: Group I (saline control), Group II (Bleomycin, given as a single intratracheal instillation, 7 U/kg) and Group III (Bleomycin + Pioglitazone (40 mg/kg/day orally, starting 7 days post bleomycin instilled as in Group II). From lung tissues, the protein expressions of IGF-1, IGFBP-5, TGF-beta 1, surfactant protein C (SP-C, as a marker for type II AECs) and alpha-smooth muscle actin (alpha-SMA, as a marker for EMT), were determined on day 7 in Groups I and II and on days 14,21 and 35 in all the three groups.Results: IGFBP-5 and IGF-1 expressions were reduced significantly and TGF-beta 1 expression increased significantly in type II AECs in Group II from day 7 till day 35 as compared to Group]. An increase in SP-C and a-SMA expression and their co-localization were seen in the type II AECs undergoing EMT from day 7 till day 35.A concomitant remodeling and laying down of ECM was observed also. In Group III, with pioglitazone, there was a reversal with significant up-regulation in IGFBP-5 and IGF-1 expressions and down-regulation of TGF-beta 1 in the type II AECs along with a significant decrease in the solid area fraction, EMT and ECM in the lung tissue.Conclusions: IGFBP-5, IGF-1 and TGF-beta 1 in the type II AECs play a key role in lung injury caused by bleomycin and pioglitazone attenuates the lung injury/fibrosis by restoring IGFBP-5 and IGF-1 and decreasing TGF-beta 1 expressions in the type II AECs. (C) 2016 Published by Elsevier Inc.