1. Hyperhomocysteinemia Accelerates Acute Kidney Injury to Chronic Kidney Disease Progression by Downregulating Heme Oxygenase-1 Expression
- Author
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Yunshi Lai, Zhanmei Zhou, Fan Yi, Bingbing Qiu, Jiajun Luo, Hong Lu, Zheng Hu, Shuang Li, Jing Nie, Shouyi Yu, Jianwei Tian, Miaomiao Zhou, Jixing Liu, and Fengxin Zhu
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Hyperhomocysteinemia ,Homocysteine ,Acute Renal Injury ,Physiology ,Biopsy ,RNA Stability ,Clinical Biochemistry ,Gene Expression ,urologic and male genital diseases ,Biochemistry ,Gastroenterology ,ELAV-Like Protein 1 ,03 medical and health sciences ,chemistry.chemical_compound ,Internal medicine ,medicine ,Renal fibrosis ,Humans ,RNA, Messenger ,Renal Insufficiency, Chronic ,Molecular Biology ,General Environmental Science ,030102 biochemistry & molecular biology ,urogenital system ,business.industry ,Acute kidney injury ,Cell Biology ,Acute Kidney Injury ,medicine.disease ,female genital diseases and pregnancy complications ,Heme oxygenase ,Kidney Tubules ,030104 developmental biology ,chemistry ,Disease Progression ,General Earth and Planetary Sciences ,Disease Susceptibility ,Reactive Oxygen Species ,business ,Heme Oxygenase-1 ,Kidney disease - Abstract
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.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.
- Published
- 2019