MAPK通路介导Prx-1抑制硅沉着病小鼠肌成纤维细胞转化

摘要
图/表
参考文献(20)
相关文章 (6)

全文: PDF (678 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的探讨丝裂原活化蛋白激酶（MAPK）通路在硫氧还蛋白过氧化物酶1（Prx-1）抗硅沉着病肌成纤维细胞转化过程中的作用。方法将40只雄性C57BL/6小鼠随机分为对照组（生理盐水）、模型组[二氧化硅（SiO2）]、转染对照组（SiO2+慢病毒载体）和Prx-1转染组（SiO2+Prx-1慢病毒）。生理盐水、SiO2及慢病毒均经支气管灌注。造模后，小鼠常规饲养12周。采用免疫组化法和免疫荧光法分别检测α-平滑肌肌动蛋白（α-SMA）及8-羟基脱氧鸟苷（8-OHdG）表达。Western blot法检测Ⅰ型、Ⅲ型胶原、Prx-1、磷酸化细胞外信号调节激酶（p-ERK1/2）、磷酸化-丝裂原活化蛋白激酶p38（P-p38）、磷酸化氨基末端激酶（p-JNK）表达。结果模型组和转染对照组可见矽结节和肺间质纤维化，但Prx-1转染组的上述病变减轻。模型组和转染对照组Prx-1表达无区别，但Prx-1转染组较模型组Prx-1表达增高。与对照组比较，其余各组肺组织α-SMA、8-OHdG、Ⅰ型及Ⅲ型胶原、p-ERK1/2、p-P38、p-JNK表达增多；与模型组和转染对照组比较，Prx-1转染组的上述指标表达减少，差异均有统计学意义（P < 0.05）。结论 Prx-1具有抑制SiO2诱导的肌成纤维细胞转化和肺纤维化作用，这种作用与降低活性氧并抑制MAPK通路活化有关。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	刘岩洪凡王朋李倩白兆荣孙影▲

关键词 ：肌成纤维细胞转化, 硫氧还蛋白过氧化物酶1, 活性氧, 丝裂原活化蛋白激酶

Abstract：Objective To investigate the role of mitogen-activated protein kinase (MAPK) pathway in the transformation of thioredoxin peroxidase-1 (Prx-1) against myofibroblasts of silicosis. Methods Forty male C57BL/6 mice were randomly divided into control group (saline), model group (SiO2), transfection control group (SiO2 + lentivirus vector) and PRX-1 transfection group (SiO2 + Prx-1 lentivirus). Normal saline, SiO2 and lentivirus were perfused through bronchus. After modeling, mice were fed for 12 weeks. Immunohistochemistry and immunofluorescence were used to detect the expression of α-smooth muscle actin (α-SMA) and 8-hydroxydeoxyguanosine (8-OHdG) respectively. Western blot was used to detect the expression of collagen type Ⅰ, collagen type Ⅲ, Prx-1, phosphorylated extracellular signal-regulated kinase (p-ERK1/2), phosphorylated-mitogen-activated protein kinase p38 (P-p38) and phosphorylated amino-terminal kinase (p-JNK). Results Silicon nodules and pulmonary interstitial fibrosis were found in model group and transfection control group, but the lesions were alleviated in Prx-1 transfection group. There was no difference in Prx-1 expression between model group and transfection control group, but compared with model group, Prx-1 expression increased in Prx-1 transfection group. Compared with control group, the expression of α-SMA, 8-OHdG, collagen type Ⅰ and collagen type Ⅲ, p-ERK1/2, p-P38 and p-JNK were increased in lung tissue of the other groups. Compared with the model group and the transfection control group, the expression of the above indicators in the Prx-1 transfection group were decreased. Conclusion Prx-1 can inhibit SiO2-induced myofibroblast transformation and pulmonary fibrosis, which is related to the reduction of oxygen-active substances and the inhibition of activation of MAPK pathway.

Key words： Myofibroblast transformation Thioredoxin peroxidase 1 Reactive oxygen species Mitogen-activated protein kinase

基金资助:河北省自然科学基金面上项目（H2016209272）；
华北理工大学杰出青年基金项目（JP201507）。

通讯作者: ▲通讯作者

引用本文:

刘岩洪凡王朋李倩白兆荣孙影▲. MAPK通路介导Prx-1抑制硅沉着病小鼠肌成纤维细胞转化[J]. 中国医药导报, 2019, 16(10): 25-29.
LIU Yan HONG Fan WANG Peng LI Qian BAI Zhaorong SUN Ying▲. MAPK pathway mediates the ability of Prx-1 to inhibite myofibroblast transformation in mice with silicosis. 中国医药导报, 2019, 16(10): 25-29.

链接本文:

http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2019/V16/I10/25

[1] 徐洪.Ac-SDKP抗矽肺纤维化作用的新靶向-肌成纤维细胞分化和差异蛋白的筛选[D].石家庄：河北医科大学，2012.
[2] Montorfano I，Becerra A，Cerro R，et al. Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway [J]. Lab Invest，2014，94（10）：1068-1082.
[3] Tobar N，Toyos M，Urra C，et al. c-Jun N terminal kinase modulates NOX-4 derived ROS production and myofibroblasts differentiation in human breast stromal cells [J]. BMC Cancer，2014，14：640-648.
[4] 贾艳春，刘英宇，魏中秋，等.硫氧环蛋白过氧化物酶1对矽肺大鼠肺纤维化的影响[J].安徽医科大学学报，2017， 52（5）：705-709.
[5] 孟令平，王国光，胡明秀，等.大鼠肝纤维化和肝硬化MR-PWI参数与CD34和a-SMA的相关性[J].放射学实践，2016，31（7）：580-585.
[6] Ma-On C，Sanpavat A，Whongsiri P，et al. Oxidative stress indicated by elevated expression of Nrf2 and 8-OHdG promotes hepatocellular carcinoma progression [J]. Med Oncol，2017，34（4）：57-64.
[7] Liu Y，Xu H，Geng YC，et al. Dibutyryl-cAMP attenuates pulmonary fibrosis by blocking myofibroblast differentiation via PKA/CREB/CBP signaling in rats with silicosis [J]. Respir Res，2017，38：38-49.
[8] 肖程程，张杰.肾纤维化的细胞和分子基础[J].中国医药导报，2017，14（7）：45-48.
[9] Vancheri C，Gili E，Failla M，et al. Bradykinin differentiates human lung fibroblasts to myofibroblast phenotype via the B2 receptor [J]. J Allergy Clin Immunol，2005，116（6）：1242-1248.
[10] Park YJ，Lee SR，Kim DM，et al. The Inhibitory Effects of Cyclodepsipeptides from the Entomopathogenic Fungus Beauveria bassiana on Myofibroblast Differentiation in A549 Alveolar Epithelial Cells [J]. Molecules，2018， 23（10）：46-58.
[11] Lai JM，Zhang X，Liu FF，et al. Redox-sensitive MAPK and Notch3 regulate fibroblast differentiation and activation：a dual role of ERK1/2 [J]. Oncotarget，2016，7（28）：43 731-43 745.
[12] Wu X，Liu Y，An J，et al. Piperlongumine inhibits angiotensin Ⅱ-induced extracellular matrix expression in cardiac fibroblasts [J]. J Cell Biochem，2018，119（12）：10 358-10 364.
[13] Thannickal VJ，Day RM，Klinz SG，et al. Ras-dependent and -independent regulation of reactive oxygen species by mitogenic growth factors and TGF-beta1 [J]. Faseb J，2000，14（12）：1741-1748.
[14] 张钊，孙影.活性氧和硫氧环蛋白过氧化物酶2在矽肺纤维化中的作用[J].包头医学院学报，2017，33（11）：131-133.
[15] Barbara LH，Monica N，John JS，et al. A Peroxidase Peroxiredoxin 1-Specific Redox Regulation of the Novel FOXO3 microRNA Target let-7 [J]. Antioxid Redox Signal，2018，28（1）：62-77.
[16] Sun X，Kong L，Li B，et al. Peroxiredoxin 1 silencing inhibited the growth and promoted apoptosis of pancreatic cancer cells via targeting FOXO3 gene [J]. Cancer Manag Res，2018，10：5019-5026.
[17] Liu X，Wang L，Cai J，et al. N-acetylcysteine alleviates H2O2-induced damage via regulating the redox status of intracellular antioxidants in H9c2 cells [J]. Int J Mol Med，2018，43（1）：199-208.
[18] 刘宝欣，刘英宇，魏中秋，等.Peroxiredoxin-1基因沉默对转化生长因子β1促进肺成纤维细胞Ⅰ、Ⅲ型胶原合成的影响[J].重庆医学，2016，45（29）：4099-4102.
[19] 刘宝欣，刘英宇，梁婷婷，等.Prx-1基因沉默对TGF-β1诱导肺成纤维细胞增殖、ROS水平、p-AKT蛋白表达的影响[J].山东医药，2016，56（7）：17-19.
[20] 孙影，贾艳春，魏中秋，等.细胞外信号调节激酶1/2通路在Peroxiredoxin-1抑制转化生长因子-β1诱导的Ⅰ、Ⅲ型胶原蛋白表达中的作用[J].中国现代医学杂志，2015，25（26）：7-11.