Reactive oxygen species modulator 1 regulates oxidative stress and induces renal and pulmonary fibrosis in a unilateral ureteral obstruction rat model and in HK‑2 cells.

Reactive oxygen species modulator 1 regulates oxidative stress and induces renal and pulmonary fibrosis in a unilateral ureteral obstruction rat model and in HK‑2 cells.
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DOI:
10.3892/mmr.2017.7161
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发表时间:
2017-10
影响因子:
3.4
通讯作者:
Yi Z
Yi Z
中科院分区:
医学4区
文献类型:
--
作者:
Liu D;Liu Y;Xia Z;Dong H;Yi Z

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肾间质纤维化(RIF)是导致肾功能衰竭的主要过程。因此,有必要对RIF的发生机制进行深入研究,并寻找合适的调控方法。采用组织病理学方法检测与肾和肺功能障碍相关的形态学损害。随后,在血清中测量活性氧(ROS)调节剂1(ROMO 1)和ROS的高表达。采用逆转录-定量聚合酶链反应(RT-PCR)和蛋白质印迹法(Western blotting)检测上皮-间质转化标志物、转化生长因子β(TGF-β)和母亲对十二指肠麻痹同系物2/3表达的影响。使用三种常用抗氧化剂进行抗氧化剂干预后,所有严重症状均得到一定程度的缓解。HK-2细胞用H2 O2处理引起氧化应激,ROMO 1和纤维化标志物表达增加;然而,ROMO 1敲除抑制了活化。本研究提供了ROMO 1的表达诱导ROS产生并激活TGF-β信号通路的证据。因此,ROMO 1基因的表达有助于为临床干预和患者预后的改善提供分子基础。
Renal interstitial fibrosis (RIF) is the main process that leads to renal failure. It is necessary to investigate the mechanism of RIF and identify appropriate methods of regulating it. Furthermore, unilateral ureteral obstruction is a frequently used model for the study of RIF. The morphological damage associated with kidney and lung dysfunction was detected using histopathological experiments. Subsequently, high expression of reactive oxygen species (ROS) modulator 1 (ROMO1) and ROS was measured in blood serum. In addition, epithelial-mesenchymal transition marker, transforming growth factor β (TGF-β) and mothers against decapentaplegic homolog 2/3 expression was evaluated using the reverse transcription-quantitative polymerase chain reaction and western blotting. All serious symptoms were relieved to a certain extent following oxidation inhibitor intervention using three common antioxidants. HK-2 cells were treated with H2O2 to cause oxidative stress, and ROMO1 and fibrosis marker expression increased; however, activation was suppressed byROMO1 knockout. The present study provides evidence that the expression of ROMO1 induces ROS production and activates the TGF-β signaling pathway. It may be concluded that ROMO1 helps to provide a molecular basis for improved clinical intervention and prognosis of patients.
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