دورية أكاديمية
NADPH oxidase 4 mediates TGF-β1/Smad signaling pathway induced acute kidney injury in hypoxia.
العنوان: | NADPH oxidase 4 mediates TGF-β1/Smad signaling pathway induced acute kidney injury in hypoxia. |
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المؤلفون: | Sungkwon Cho, Seong-Lan Yu, Jaeku Kang, Bo Young Jeong, Hoi Young Lee, Chang Gyo Park, Young-Bin Yu, Dong-Chan Jin, Won-Min Hwang, Sung-Ro Yun, Ho Seung Song, Moon Hyang Park, Se-Hee Yoon |
المصدر: | PLoS ONE, Vol 14, Iss 7, p e0219483 (2019) |
بيانات النشر: | Public Library of Science (PLoS), 2019. |
سنة النشر: | 2019 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | Hypoxia is an important cause of acute kidney injury (AKI) in various conditions because kidneys are one of the most susceptible organs to hypoxia. In this study, we investigated whether nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase 4 (Nox4) plays a role in hypoxia induced AKI in a cellular and animal model. Expression of Nox4 in cultured human renal proximal tubular epithelial cells (HK-2) was significantly increased by hypoxic stimulation. TGF-β1 was endogenously secreted by hypoxic HK-2 cells. SB4315432 (a TGF-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells through the Smad-dependent cell signaling pathway. Silencing of Nox4 using Nox4 siRNA and pharmacologic inhibition with GKT137831 (a specific Nox1/4 inhibitor) reduced the production of ROS and attenuated the apoptotic pathway. In addition, knockdown of Nox4 increased cell survival in hypoxic HK-2 cells and pretreatment with GKT137831 reproduce these results. This study demonstrates that hypoxia induces HK-2 cell apoptosis through a signaling pathway involving TGF-β1 via Smad pathway induction of Nox4-dependent ROS generation. In an ischemia/reperfusion rat model, pretreatment of GKT137831 attenuated ischemia/reperfusion induced acute kidney injury as indicated by preserved kidney function, attenuated renal structural damage and reduced apoptotic cells. Therapies targeting Nox4 may be effective against hypoxia-induced AKI. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 |
Relation: | https://doaj.org/toc/1932-6203 |
DOI: | 10.1371/journal.pone.0219483 |
URL الوصول: | https://doaj.org/article/6a1a4c0b2c444dbfbca7d20b43bab9f6 |
رقم الأكسشن: | edsdoj.6a1a4c0b2c444dbfbca7d20b43bab9f6 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 |
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DOI: | 10.1371/journal.pone.0219483 |