标题:Hyperhomocysteinemia Accelerates Acute Kidney Injury to Chronic Kidney Disease Progression by Downregulating Heme Oxygenase-1 Expression
作者:Li, Shuang; Qiu, Bingbing; Lu, Hong; Lai, Yunshi; Liu, Jixing; Luo, Jiajun; Zhu, Fengxin; Hu, Zheng; Zhou, Miaomiao; Tian, Jianwei; 更多
作者机构:[Li, Shuang; Qiu, Bingbing; Lai, Yunshi; Liu, Jixing; Luo, Jiajun; Zhu, Fengxin; Hu, Zheng; Zhou, Miaomiao; Tian, Jianwei; Zhou, Zhanmei; Nie, Jing] S 更多
通讯作者:Nie, J
通讯作者地址:[Nie, J]Southern Med Univ, State Key Lab Organ Failure Res, Natl Clin Res Ctr Kidney Dis,Nanfang Hosp, Key Lab Organ Failure Res,Minist Educ,Div Nephr 更多
来源:ANTIOXIDANTS & REDOX SIGNALING
出版年:2018
DOI:10.1089/ars.2017.7397
关键词:homocysteine; acute renal injury; renal fibrosis; heme oxygenase-1; HuR
摘要:Aims: The risk factors promoting acute kidney injury (AKI) to chronic kidney disease (CKD) progression remain largely unknown. The aim of the present study was to investigate whether hyperhomocysteinemia (Hhcy) accelerates the development of renal fibrosis after AKI. Results: Hhcy aggravated ischemia-reperfusion-induced AKI and the subsequent development of renal fibrotic lesions characterized by excessive extracellular matrix deposition. Mechanistically, the RNA binding protein human antigen R (HuR) bound to the 3-untranslated region (3-UTR) of heme oxygenase-1 (HO-1) messenger RNA (mRNA). Homocysteine (Hcy) downregulated HuR expression, reduced the binding of HuR to the 3-UTR of HO-1, and thereafter decreased HO-1 expression. Administration of the HO-1 inducer cobalt protoporphyrin-IX significantly hindered Hhcy-augmented reactive oxygen species production and renal fibrotic lesions. Innovation and Conclusion: These data indicate that Hhcy might be a novel risk factor that promotes AKI to CKD progression. Lowering Hcy level or HO-1 induction might be a potential therapeutic strategy to improve the outcome of AKI. Antioxid. Redox Signal. 00, 000-000.
收录类别:SCIE
资源类型:期刊论文
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