MnTBAP Inhibits Bleomycin-Induced Pulmonary Fibrosis by Regulating VEGF and Wnt Signaling.
MnTBAP Inhibits Bleomycin-Induced Pulmonary Fibrosis by Regulating VEGF and Wnt Signaling.
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DOI：
10.1002/jcp.25608
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发表时间：
2017-03
影响因子：
5.6
通讯作者：
Azad N
中科院分区：
文献类型：
--
作者：
Venkatadri R;Iyer AK;Ramesh V;Wright C;Castro CA;Yakisich JS;Azad N
细胞氧化应激不仅与肺损伤有关，而且与肺纤维化的发展有关。我们表明，细胞渗透性超氧化物歧化酶（SOD）模拟和过氧亚硝酸根清除剂，锰（III）四（4-苯甲酸）卟啉氯化物（MnTBAP）显着抑制博莱霉素诱导的纤维化作用在体外和体内。对潜在机制的进一步研究表明，MnTBAP靶向经典Wnt和非经典Wnt/Ca 2+信号通路，这两者都被博来霉素处理上调。MnTBAP对经典Wnt信号传导的影响在体内是显著的，但在体外是不确定的，并且观察到非经典Wnt/Ca 2+信号传导途径是由MnTBAP在博莱霉素诱导的肺纤维化中调节的主要途径。此外，我们发现MnTBAP的抑制作用涉及调节VEGF，其是Wnt信号通路的上游。总体而言，数据显示，超氧化物清除剂MnTBAP通过靶向VEGF和Wnt信号传导途径减弱博来霉素诱导的肺纤维化。
Cellular oxidative stress is implicated not only in lung injury but also in contributing to the development of pulmonary fibrosis. We demonstrate that a cell-permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger, manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) significantly inhibited bleomycin-induced fibrogenic effects both in vitro and in vivo. Further investigation into the underlying mechanisms revealed that MnTBAP targets canonical Wnt and non-canonical Wnt/Ca2+ signaling pathways, both of which were upregulated by bleomycin treatment. The effect of MnTBAP on canonical Wnt signaling was significant in vivo but inconclusive in vitro and the non-canonical Wnt/Ca2+ signaling pathway was observed to be the predominant pathway regulated by MnTBAP in bleomycin-induced pulmonary fibrosis. Furthermore, we show that the inhibitory effects of MnTBAP involve regulation of VEGF which is upstream of the Wnt signaling pathway. Overall, the data show that the superoxide scavenger MnTBAP attenuates bleomycin-induced pulmonary fibrosis by targeting VEGF and Wnt signaling pathways.
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影响因子：
3.4
作者：
Kulkarni YM;Dutta S;Iyer AK;Venkatadri R;Kaushik V;Ramesh V;Wright CA;Semmes OJ;Yakisich JS;Azad N
通讯作者：
Azad N
DOI：
10.1152/ajplung.00183.2015
发表时间：
2016-05-15
影响因子：
4.9
作者：
Fernandez, Isis E.;Amarie, Oana V.;Eickelberg, Oliver
通讯作者：
Eickelberg, Oliver
影响因子：
2
作者：
Jessen, Jason R.
通讯作者：
Jessen, Jason R.
DOI：
10.1016/j.biocel.2013.04.003
发表时间：
2013-07-01
影响因子：
4
作者：
Deng, Xiaoling;Xu, Mingyan;Pang, Linhua
通讯作者：
Pang, Linhua
影响因子：
4
作者：
Iyer AK;Ramesh V;Castro CA;Kaushik V;Kulkarni YM;Wright CA;Venkatadri R;Rojanasakul Y;Azad N
通讯作者：
Azad N