Evidence map›Paper›PMID 41332335›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Inactivation of AXL in Cardiac Fibroblasts Alleviates Right Ventricular Remodeling in Pulmonary Hypertension.

Li-Wei Wu, Min Chen, Chen-Yu Jiang, Dai-Ji Jiang, Xu Zhang, Xiao-He Xu, Yi-Wei Liu, Bei Feng, Lin-Cai Ye, Yang-Yang He and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

18 authors.

Li-Wei WuHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Min ChenChildren's Heart Center, Institute of Cardiovascular Development and Translational Medicine, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
Chen-Yu JiangHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Dai-Ji JiangHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Xu ZhangHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Xiao-He XuSchool of Pharmacy, Henan University, Kaifeng, 475004, China.
Yi-Wei LiuHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Bei FengHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Lin-Cai YeHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Yang-Yang HeSchool of Pharmacy, Henan University, Kaifeng, 475004, China.
Xu HuangHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Yi-Chi ZhangHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Xing-Liang ZhouHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Yi ShenHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Tian-Yu LiuHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Li-Jun FuHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Yi YanHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.ORCID https://orcid.org/0000-0003-2860-3252
Hao ZhangHeart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

Funding

Innovative Research Team of High-level Local University in ShanghaiNational Clinical Key Specialty Construction Project 10000015Z155080000004Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0526700Outstanding Youth Fund Project of Henan Natural Science Foundation 252300421026Project of National Natural Science Foundation of China 82200065Project of National Natural Science Foundation of China U20A2018Project of Shanghai Municipal Science and Technology Commission 23Y31900600Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics 20dz2260900Shanghai Key Research Center Construction Project-Shanghai Research Center for Pediatric Cardiovascular Diseases 2023ZZ02024Technology Innovation Talent Support Program for Higher Education in Henan Province 25HASTIT056Wellcome Trust 202404Young Talent Program of Shanghai Municipal Health Commission 2022YQ070
6 · The paper itself

Abstract

Right ventricular (RV) adaptation critically determines survival in pulmonary hypertension (PH). Since cardiac fibroblasts (FBs) are crucial mediators of cardiac fibrosis, we aim to uncover the mechanism underlying their activation during RV remodeling. Using single-nucleus RNA sequencing (snRNA-seq) across three rodent PH models-hypobaric hypoxia and Sugen 5416/hypoxia in mice, and monocrotaline in rats-we identified elevated Axl expression in RV FBs under PH. AXL upregulation was consistently observed in RV FBs from both human PH patients and animal models. Cardiac FB-specific Axl overexpression exacerbated RV remodeling in both PH and pulmonary artery banding (PAB) models, whereas Axl knockdown in FBs alleviated this remodeling. Functionally, AXL promoted FB proliferation, migration, and extracellular matrix synthesis via the PI3K-AKT pathway, facilitating nuclear translocation of NFIC, which in turn promoted the transcription of targeted genes such as COL1A1. Inhibiting PI3K or administering R428 mitigated AXL-driven RV remodeling in PH, and R428 also ameliorated remodeling in PAB mice. In conclusion, AXL signals the PI3K-AKT pathway to license nuclear translocation of NFIC, thereby dictating the transcription of fibrotic genes in FBs and driving RV remodeling. These findings reveal novel insights into RV pathophysiology and highlight AXL as a potential therapeutic target for PH-induced RV remodeling.

Indexed as

FibroblastsHypertension, PulmonaryProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesVentricular RemodelingAnimalsAxl Receptor Tyrosine KinaseDisease Models, AnimalHumansMaleMiceMyocardiumRatsSignal TransductionAxl Receptor Tyrosine KinaseProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesAXLpulmonary hypertensionright ventricular remodelingsingle‐nucleus RNA sequencingtranscription factor nuclear factor I C

Identifiers

PMID41332335
PMCPMC12903973

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.