Evidence map›Paper›PMID 36915149›Full record

ArticleRespiratory research2023

Circ-Ntrk2 acts as a miR-296-5p sponge to activate the TGF-β1/p38 MAPK pathway and promote pulmonary hypertension and vascular remodelling.

Lihuang Su, Xiuchun Li, Xulong Mao, Tingting Xu, Yiying Zhang, Shini Li, Xiayan Zhu, Liangxing Wang, Dan Yao, Jian Wang and 1 more

Open access · goldFull text read
In one paragraph

Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. CircRNA-mediated regulation of cardiovascular disease.Frontiers in cardiovascular medicine · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Lihuang Su *Division of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Xiuchun Li *Division of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Xulong Mao *Division of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Tingting XuDivision of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Yiying ZhangDivision of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Shini LiDivision of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Xiayan ZhuDivision of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Liangxing WangDivision of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Dan YaoDivision of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. zdyaodan@163.com.
Jian WangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, Guangdong, China. jiw037@health.ucsd.edu.
Xiaoying HuangDivision of Pulmonary Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. huangxiaoying@wzhospital.cn.
Wenzhou Medical University · CNFirst Affiliated Hospital of Wenzhou Medical University · CNState Key Laboratory of Respiratory Disease · CN

Funding

Basic scientific research Project of Wenzhou H20210010National Natural Science Foundation of China 82170061
6 · The paper itself

Abstract

backgroundCircular RNAs (circRNAs), a novel class of non-coding RNAs, play an important regulatory role in pulmonary arterial hypertension (PAH); however, the specific mechanism is rarely studied. In this study, we aimed to discover functional circRNAs and investigate their effects and mechanisms in hypoxia-induced pulmonary vascular remodelling, a core pathological change in PAH.

methodsRNA sequencing was used to illustrate the expression profile of circRNAs in hypoxic PAH. Bioinformatics, Sanger sequencing, and quantitative real-time PCR were used to identify the ring-forming characteristics of RNA and analyse its expression. Then, we established a hypoxia-induced PAH mouse model to evaluate circRNA function in PAH by echocardiography and hemodynamic measurements. Moreover, microRNA target gene database screening, fluorescence in situ hybridisation, luciferase reporter gene detection, and western blotting were used to explore the mechanism of circRNAs.

resultsRNA sequencing identified 432 differentially expressed circRNAs in mouse hypoxic lung tissues. Our results indicated that circ-Ntrk2 is a stable cytoplasmic circRNA derived from Ntrk2 mRNA and frequently upregulated in hypoxic lung tissue. We further found that circ-Ntrk2 sponges miR-296-5p and miR-296-5p can bind to the 3'-untranslated region of transforming growth factor-β1 (TGF-β1) mRNA, thereby attenuating TGF-β1 translation. Through gene knockout or exogenous expression, we demonstrated that circ-Ntrk2 could promote PAH and vascular remodelling. Moreover, we verified that miR-296-5p overexpression alleviated pulmonary vascular remodelling and improved PAH through the TGF-β1/p38 MAPK pathway.

conclusionsWe identified a new circRNA (circ-Ntrk2) and explored its function and mechanism in PAH, thereby establishing potential targets for the diagnosis and treatment of PAH. Furthermore, our study contributes to the understanding of circRNA in relation to PAH.

Indexed as

Hypertension, PulmonaryMicroRNAsPulmonary Arterial HypertensionRNA, CircularAnimalsCell ProliferationFamilial Primary Pulmonary HypertensionMiceReceptor, trkBRNA, MessengerTransforming Growth Factor beta1Vascular RemodelingMicroRNAsMIRN296 microRNA, mouseNtrk2 protein, mouseReceptor, trkBRNA, CircularRNA, MessengerTransforming Growth Factor beta1Circ-Ntrk2miR-296-5pProliferationPulmonary arterial hypertensionRight ventricular hypertrophyVascular remodelling

Identifiers

PMID36915149
PMCPMC10012448
OpenAlexW4324054948

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read34
table measurements read2
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.