PMID- 30084650
OWN - NLM
STAT- MEDLINE
DCOM- 20200702
LR  - 20200702
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Linking)
VI  - 30
IP  - 13
DP  - 2019 May 1
TI  - Hyperhomocysteinemia Accelerates Acute Kidney Injury to Chronic Kidney Disease 
      Progression by Downregulating Heme Oxygenase-1 Expression.
PG  - 1635-1650
LID - 10.1089/ars.2017.7397 [doi]
AB  - 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.
FAU - Li, Shuang
AU  - Li S
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Qiu, Bingbing
AU  - Qiu B
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Lu, Hong
AU  - Lu H
AD  - 2 Department of Public Health, School of Public Health, Southern Medical 
      University, Guangzhou, China.
FAU - Lai, Yunshi
AU  - Lai Y
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Liu, Jixing
AU  - Liu J
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Luo, Jiajun
AU  - Luo J
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Zhu, Fengxin
AU  - Zhu F
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Hu, Zheng
AU  - Hu Z
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Zhou, Miaomiao
AU  - Zhou M
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Tian, Jianwei
AU  - Tian J
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Zhou, Zhanmei
AU  - Zhou Z
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Yu, Shouyi
AU  - Yu S
AD  - 2 Department of Public Health, School of Public Health, Southern Medical 
      University, Guangzhou, China.
FAU - Yi, Fan
AU  - Yi F
AD  - 3 Department of Pharmacology, Shandong University School of Medicine, Jinan, 
      China.
FAU - Nie, Jing
AU  - Nie J
AD  - 1 State Key Laboratory of Organ Failure Research, National Clinical Research 
      Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of 
      Education), Division of Nephrology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180918
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (ELAV-Like Protein 1)
RN  - 0 (ELAVL1 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Acute Kidney Injury/etiology/*metabolism/*pathology
MH  - Biopsy
MH  - Disease Progression
MH  - Disease Susceptibility
MH  - ELAV-Like Protein 1/metabolism
MH  - Gene Expression
MH  - Heme Oxygenase-1/*genetics/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/blood/complications/*metabolism
MH  - Kidney Tubules/metabolism
MH  - RNA Stability
MH  - RNA, Messenger/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Renal Insufficiency, Chronic/etiology/*metabolism/*pathology
OTO - NOTNLM
OT  - HuR
OT  - acute renal injury
OT  - heme oxygenase-1
OT  - homocysteine
OT  - renal fibrosis
EDAT- 2018/08/08 06:00
MHDA- 2020/07/03 06:00
CRDT- 2018/08/08 06:00
PHST- 2018/08/08 06:00 [pubmed]
PHST- 2020/07/03 06:00 [medline]
PHST- 2018/08/08 06:00 [entrez]
AID - 10.1089/ars.2017.7397 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2019 May 1;30(13):1635-1650. doi: 10.1089/ars.2017.7397. 
      Epub 2018 Sep 18.