کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8258646 | 1534611 | 2018 | 42 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Induction of cytochrome P450 4A14 contributes to angiotensin II-induced renal fibrosis in mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Angiotensin II (AngII) plays an important role in the pathogenesis of hypertension and associated renal injuries. To elucidate the molecular mechanism by which AngII induces renal damage, we found that AngII infusion significantly induced CYP4A14 expression in renal proximal tubule cells (RPTCs) with marked increases in blood pressure and proteinuria. Renal production of the major CYP4A metabolite, 20-HETE, was also significantly increased in the AngII-treated mice. Compared to wild-type (WT) mice, CYP4A14 knockout (CYP4A14â/â) mice exhibited significantly lower levels of blood pressure, renal 20-HETE production, proteinuria and renal fibrosis following AngII infusion. Furthermore, AngII-induced renal expression of profibrotic genes and proinflammatory genes was significantly attenuated in CYP4A14â/â mice. In vitro studies using cultured RPTCs demonstrated that AngII significantly induced CYP4A14 expression and 20-HETE production via the MAPK signaling pathway. AngII treatment increased TGF-β and collagen expression, which was attenuated by the CYP4A inhibitor, TS-011. Moreover, 20-HETE treatment potently induced CYP4A14 expression and TGF-β and collagen levels. Collectively, these findings suggest that attenuated renal fibrosis in AngII-treated CYP4A14â/â mice may result from both reduced systemic blood pressure and renal 20-HETE production. Therefore, CYP4A14 may represent a useful target for the treatment of AngII-associated renal damage.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 3, March 2018, Pages 860-870
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 3, March 2018, Pages 860-870
نویسندگان
Yunfeng Zhou, Jingwei Yu, Jia Liu, Rong Cao, Wen Su, Sha Li, Shiqi Ye, Chenggang Zhu, Xiaolin Zhang, Hu Xu, Hua Chen, Xiaoyan Zhang, Youfei Guan,