RGD Reference Report - Positive feedback-loop of telomerase reverse transcriptase and 15-lipoxygenase-2 promotes pulmonary hypertension. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Positive feedback-loop of telomerase reverse transcriptase and 15-lipoxygenase-2 promotes pulmonary hypertension.

Authors: Shen, T  Ma, J  Zhang, L  Yu, X  Liu, M  Hou, Y  Wang, Y  Ma, C  Li, S  Zhu, D 
Citation: Shen T, etal., PLoS One. 2013 Dec 23;8(12):e83132. doi: 10.1371/journal.pone.0083132. eCollection 2013.
RGD ID: 11038675
Pubmed: PMID:24376652   (View Abstract at PubMed)
PMCID: PMC3871619   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0083132   (Journal Full-text)

OBJECTIVE: Pulmonary hypertension (PH) is characterized with pulmonary vasoconstriction and vascular remodeling mediated by 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) according to our previous studies. Meanwhile, telomerase reverse transcriptase (TERT) activity is highly correlated with vascular injury and remodeling, suggesting that TERT may be an essential determinant in the development of PH. The aim of this study was to determine the contribution and molecular mechanisms of TERT in the pathogenesis of PH. APPROACH AND RESULTS: We measured the right ventricular systolic pressure (RVSP) and ventricular weight, analyzed morphometric change of the pulmonary vessels in the hypoxia or monocrotaline treated rats. Bromodeoxyuridine incorporation, transwell assay and flow cytometry in pulmonary smooth muscle cells were performed to investigate the roles and relationship of TERT and 15-LO/15-HETE in PH. We revealed that the expression of TERT was increased in pulmonary vasculature of patients with PH and in the monocrotaline or hypoxia rat model of PH. The up-regulation of TERT was associated with experimental elevated RVSP and pulmonary vascular remodeling. Coimmunoprecipitation experiments identified TERT as a novel interacting partner of 15-LO-2. TERT and 15-LO-2 augmented protein expression of each other. In addition, the proliferation, migration and cell-cycle transition from G0/G1 phase to S phase induced by hypoxia were inhibited by TERT knockdown, which were rescued by 15-HETE addition. CONCLUSIONS: These results demonstrate that TERT regulates pulmonary vascular remodeling. TERT and 15-LO-2 form a positive feedback loop and together promote proliferation and migration of pulmonary artery smooth muscle cells, creating a self-amplifying circuit which propels pulmonary hypertension.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Tert  (telomerase reverse transcriptase)

Genes (Mus musculus)
Tert  (telomerase reverse transcriptase)

Genes (Homo sapiens)
TERT  (telomerase reverse transcriptase)


Additional Information