Evidence map›Paper›PMID 41671391›Full record

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

Inactivation Rap2a in Endothelial Cell Prevents Pulmonary Fibrosis by Regulating Immune Microenvironment Through MAP4K4-VCAM1 Signaling.

Xiaolan Zheng, Peng Yue, Kaiyu Zhou, Guidong Gong, Yue Zhang, Sha Lin, Xu Liu, Yanjiang Zheng, Siyuan Jing, Junling Guo and 4 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. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Xiaolan ZhengKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Peng YueKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Kaiyu ZhouKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Guidong GongInstitute of Cardiovascular Surgery, The Second Affiliated Hospital, Army Medical University, Chongqing, China.
Yue ZhangKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Sha LinKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Xu LiuKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Yanjiang ZhengKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Siyuan JingKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Junling GuoBMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, China.
Yan QiState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, Hubei, China.
Bi-Sen DingKey Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, West China School of Basic Medical Sciences & Forensic Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Yimin HuaKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Yifei LiKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0002-3096-4287

Funding

National Natural Science Foundation of China 82270249National Natural Science Foundation of China 82570290Open Research Fund Program of the State Key Laboratory of Biocatalysis and Enzyme Engineering SKLBEE2021008Technology Project of Sichuan Province of China 2024YFFK0078Technology Project of Sichuan Province of China 2024YFFK0367
6 · The paper itself

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrotic remodeling accompanied by persistent endothelial activation and leukocyte infiltration. Although endothelial dysfunction is increasingly recognized as a key contributor to fibrogenesis, the intracellular signaling pathways that couple inflammatory cues to endothelial-immune interactions remain incompletely defined. Ras-related protein Rap2a (RAP2A), a small GTPase implicated in stress and inflammatory signaling, has not been systematically investigated in pulmonary endothelial cells during fibrotic lung injury. Here, using a bleomycin-induced experimental lung fibrosis model, we observed that RAP2A expression was markedly upregulated in pulmonary endothelial cells and correlated with disease severity. Endothelium-enriched knockdown of Rap2a via AAV9-Cdh5-shRNA attenuated inflammatory cell adhesion to the pulmonary endothelium, reduced fibrotic remodeling, and improved lung function. Mechanistically, RAP2A promoted endothelial activation by enhancing MAP4K4-dependent signaling and upregulating vascular cell adhesion molecule 1 (VCAM1) in response to pro-inflammatory stimulation, thereby facilitating leukocyte-endothelial interactions. In vitro assays further demonstrated that RAP2A deficiency impaired tumor necrosis factor-α-induced endothelial adhesiveness without affecting basal endothelial integrity. Collectively, our findings identify endothelial RAP2A as a regulator of inflammatory endothelial activation in experimental lung fibrosis and suggest that targeting RAP2A-mediated signaling may represent a potential strategy to modulate endothelial-immune crosstalk during fibrotic lung injury.

Indexed as

Endothelial CellsIdiopathic Pulmonary FibrosisProtein Serine-Threonine KinasesPulmonary Fibrosisrap GTP-Binding ProteinsVascular Cell Adhesion Molecule-1AnimalsBleomycinDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLSignal TransductionBleomycinProtein Serine-Threonine KinasesRAP2A protein, humanrap GTP-Binding ProteinsVascular Cell Adhesion Molecule-1CellNexendothelial cellsimmune microenvironmentpulmonary fibrosisRap2a

Identifiers

PMID41671391
PMCPMC13088280

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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.