PMID- 28445205
OWN - NLM
STAT- MEDLINE
DCOM- 20180319
LR  - 20181202
IS  - 1473-5598 (Electronic)
IS  - 0263-6352 (Print)
IS  - 0263-6352 (Linking)
VI  - 35
IP  - 9
DP  - 2017 Sep
TI  - Inhibition of microRNA-429 in the renal medulla increased salt sensitivity of 
      blood pressure in Sprague Dawley rats.
PG  - 1872-1880
LID - 10.1097/HJH.0000000000001373 [doi]
AB  - BACKGROUND: We have previously shown that high salt intake suppresses the 
      expression of prolyl hydroxylase domain-containing protein 2 (PHD2), an enzyme 
      promoting the degradation of hypoxia-inducible factor (HIF)-1alpha, and increases 
      HIF-1alpha along with its target genes in the renal medulla, which promotes sodium 
      excretion and regulates salt sensitivity of blood pressure. However, it remains 
      unknown how high salt inhibits the expression of PHD2. METHOD AND RESULTS: The 
      current study first revealed that high-salt-induced PHD2 inhibition was due to 
      the enhanced decay of mRNA. We then found that high salt significantly increased 
      the expression of miR-429, which was subsequently proven to target the 
      3'-untranslated region of PHD2 and reduce PHD2 levels, in the renal medulla. To 
      define the functional role of renal medullary miR-429 in the regulation of 
      PHD2/HIF-1alpha-mediated renal adaptation to high salt intake and salt sensitivity of 
      blood pressure, we locally inhibited miR-429 in the renal medulla by locked 
      nucleic acid anti-miR-429 in uninephrectomized rats. Our results demonstrated 
      that inhibition of miR-429 remarkably increased the levels of PHD2, which 
      disrupted PHD2-associated adaptive activation of HIF-1alpha-mediated gene expression 
      in response to high salt in the renal medulla and consequently inhibited urinary 
      sodium excretion, enhanced sodium retention in response to chronic sodium 
      overloading, and as a result, produced a salt-sensitive hypertension. CONCLUSION: 
      It is concluded that miR-429 is an important upstream mediator in 
      PHD2/HIF-1alpha-associated renal adaptation to high salt intake and that deficiency 
      in miR-429-mediated PHD2 inhibition in response to high salt in the renal medulla 
      may represent a pathogenic mechanism for salt-sensitive hypertension.
FAU - Zhu, Qing
AU  - Zhu Q
AD  - aInstitute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, 
      China bDepartment of Pharmacology & Toxicology, Virginia Commonwealth University, 
      Medical College of Virginia Campus, Richmond, Virginia, USA cLaboratory for 
      Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal 
      University, Fuzhou, China.
FAU - Hu, Junping
AU  - Hu J
FAU - Wang, Lei
AU  - Wang L
FAU - Wang, Weili
AU  - Wang W
FAU - Wang, Zhengchao
AU  - Wang Z
FAU - Li, Pin-Lan
AU  - Li PL
FAU - Boini, Krishna M
AU  - Boini KM
FAU - Li, Ningjun
AU  - Li N
LA  - eng
GR  - R01 DK104031/DK/NIDDK NIH HHS/United States
GR  - R01 HL089563/HL/NHLBI NIH HHS/United States
GR  - R01 HL106042/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (MicroRNAs)
RN  - 451W47IQ8X (Sodium Chloride)
SB  - IM
MH  - Animals
MH  - *Blood Pressure/drug effects/genetics
MH  - *Hypertension/metabolism
MH  - *Kidney Medulla/drug effects/metabolism
MH  - *MicroRNAs/antagonists & inhibitors/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium Chloride/*pharmacology
PMC - PMC5837286
MID - NIHMS946644
COIS- Disclosure: the authors declared no conflict of interest.
EDAT- 2017/04/27 06:00
MHDA- 2018/03/20 06:00
PMCR- 2018/09/01
CRDT- 2017/04/27 06:00
PHST- 2017/04/27 06:00 [pubmed]
PHST- 2018/03/20 06:00 [medline]
PHST- 2017/04/27 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - 10.1097/HJH.0000000000001373 [doi]
PST - ppublish
SO  - J Hypertens. 2017 Sep;35(9):1872-1880. doi: 10.1097/HJH.0000000000001373.