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MnTBAP Inhibits Bleomycin‐Induced Pulmonary Fibrosis by Regulating VEGF and Wnt Signaling
Author(s) -
Venkatadri Rajkumar,
Iyer Anand Krishnan V.,
Ramesh Vani,
Wright Clayton,
Castro Carlos A.,
Yakisich Juan S.,
Azad Neelam
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25608
Subject(s) - bleomycin , wnt signaling pathway , pulmonary fibrosis , chemistry , signal transduction , superoxide dismutase , cancer research , fibrosis , microbiology and biotechnology , biology , pharmacology , oxidative stress , medicine , biochemistry , chemotherapy
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. J. Cell. Physiol. 232: 506–516, 2017. © 2016 Wiley Periodicals, Inc.