Document Detail


The microRNA-328 regulates hypoxic pulmonary hypertension by targeting at insulin growth factor 1 receptor and L-type calcium channel-α1C.
MedLine Citation:
PMID:  22392900     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic hypoxia is the most common cause of secondary pulmonary hypertension, for which the mechanisms are still unclear. Recent studies implicated an important role for microRNAs (miRNAs) in hypoxia-mediated responses in various cellular processes, including cell apoptosis and proliferation. Therefore, we hypothesized that these regulatory molecules might be implicated in the etiology of hypoxic pulmonary hypertension. Here we show that miRNA-328, a posttranscriptional regulator, was drastically downregulated in the pulmonary artery (PA) after a hypoxic assault. PA rings, Western blot, quantitative real-time PCR, in situ hybridization, and luciferase assay were used to investigate the role of miRNA-328 in hypoxic pulmonary hypertension. We found that hypoxia produced a significant inhibition of miRNA-328 expression, which was involved in PA vasoconstriction and remodeling. Overexpressing miRNA-328 in the transgenic mice remarkably decreased the right ventricular systolic pressure and PA wall thickness under both normoxia and hypoxia. MiRNA-328 inhibited L-type calcium channel-α1C expression through a miRNA-328 binding site within the 3' untranslational region of L-type calcium channel-α1C. The L-type calcium channel-α1C inhibition attenuated the PA response to KCl. Furthermore, miRNA-328 suppressed the insulin growth factor 1 receptor, ultimately leading to apoptosis of pulmonary arterial smooth muscle cells. The posttranscriptional repression of L-type calcium channel-α1C and insulin growth factor 1 receptor was further confirmed by luciferase reporter assay. These results showed that miRNA-328, an important protecting factor, plays a significant role in PA constriction and remodeling by regulating multiple gene targets in hypoxic pulmonary hypertension.
Authors:
Lei Guo; Zhaoping Qiu; Liuping Wei; Xiufeng Yu; Xu Gao; Shulin Jiang; Hai Tian; Chun Jiang; Daling Zhu
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-05
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-20     Completed Date:  2012-06-14     Revised Date:  2012-08-09    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1006-13     Citation Subset:  IM    
Affiliation:
Department of Biopharmaceutical Sciences, College of Pharmacy, Second Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, People's Republic of China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / complications,  physiopathology
Apoptosis / genetics,  physiology
Calcium Channels, L-Type / metabolism*
Disease Models, Animal
Hypertension, Pulmonary / complications,  genetics,  metabolism*,  physiopathology
Insulin-Like Growth Factor Binding Protein 1 / metabolism*
Mice
Mice, Transgenic
MicroRNAs / genetics,  metabolism*
Muscle, Smooth, Vascular / metabolism*,  physiopathology
Pulmonary Artery / pathology,  physiopathology
Random Allocation
Real-Time Polymerase Chain Reaction / methods
Reference Values
Sensitivity and Specificity
Vasoconstriction / physiology
Chemical
Reg. No./Substance:
0/Calcium Channels, L-Type; 0/Insulin-Like Growth Factor Binding Protein 1; 0/L-type calcium channel alpha(1C); 0/MIRN328 microRNA, human; 0/MicroRNAs
Comments/Corrections
Comment In:
Hypertension. 2012 Jul;60(1):e3; author reply e4   [PMID:  22689742 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Sildenafil citrate rescues fetal growth in the catechol-O-methyl transferase knockout mouse model.
Next Document:  Lectin-Like Oxidized Low-Density Lipoprotein 1 Receptor in a Reduced Uteroplacental Perfusion Pressu...