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However, the underlying molecular mechanisms induced by ROS<\/jats:styled-content> in these pathologies remain unclear. To resolve this issue, we established an in\u00a0vivo<\/jats:italic> model of ROS<\/jats:styled-content> overproduction by generating a transgenic (TG<\/jats:styled-content>) mouse line expressing the human NADPH<\/jats:styled-content> oxidase 4<\/jats:italic> (NOX<\/jats:styled-content>4, NOX<\/jats:styled-content>4\u2010<\/jats:italic>TG<\/jats:styled-content> mice), which is a constitutively active ROS<\/jats:styled-content>\u2010producing enzyme that does not require stimulation or an activator. Overproduction of ROS<\/jats:styled-content> was detected at the cochlea of the inner ear in NOX<\/jats:styled-content>4<\/jats:italic>\u2010TG<\/jats:styled-content> mice, but they showed normal hearing function under baseline conditions. However, they demonstrated hearing function vulnerability, especially at high\u2010frequency sounds, upon exposure to intense noise, which was accompanied by loss of cochlear outer hair cells (OHC<\/jats:styled-content>s). The vulnerability to loss of hearing function and OHC<\/jats:styled-content>s was rescued by treatment with the antioxidant Tempol. Additionally, we found increased protein levels of the heat\u2010shock protein 47 (HSP<\/jats:styled-content>47) in models using HEK<\/jats:styled-content>293 cells, including H2<\/jats:sub>O2<\/jats:sub> treatment and cells with stable and transient expression of NOX<\/jats:styled-content>4. Furthermore, the up\u2010regulated levels of Hsp47 were observed in both the cochlea and heart of NOX<\/jats:styled-content>4<\/jats:italic>\u2010TG<\/jats:styled-content> mice. Thus, antioxidant therapy is a promising approach for the treatment of NIHL<\/jats:styled-content>. Hsp47 may be an endogenous antioxidant factor, compensating for the chronic ROS<\/jats:styled-content> overexposure in\u00a0vivo<\/jats:italic>, and counteracting ROS<\/jats:styled-content>\u2010related hearing loss.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14451","type":"journal-article","created":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T07:43:33Z","timestamp":1524210213000},"page":"459-473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Hearing vulnerability after noise exposure in a mouse model of reactive oxygen species overproduction"],"prefix":"10.1111","volume":"146","author":[{"given":"Shigefumi","family":"Morioka","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology Biosignal Research Center Kobe University Kobe Japan"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery 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