Hyperhomocysteinemia Accelerates Acute Kidney Injury to Chronic Kidney Disease Progression by Downregulating Heme Oxygenase-1 Expression.

Abstract:

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.

journal_name

Antioxid Redox Signal

authors

Li S,Qiu B,Lu H,Lai Y,Liu J,Luo J,Zhu F,Hu Z,Zhou M,Tian J,Zhou Z,Yu S,Yi F,Nie J

doi

10.1089/ars.2017.7397

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

1635-1650

issue

13

eissn

1523-0864

issn

1557-7716

journal_volume

30

pub_type

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