Evidence map›Paper›PMID 42539123›Full record

ArticlebioRxiv : the preprint server for biology2026

CXCL12/CXCR4 Governs Lymphatic Valve Formation Through Flow Dependent AKT/FOXO1/FOXC2 Activation.

Long Nguyen Hoang Do, Jingjing Pang, Esteban Delgado, Liam Flynn, Hongxia Liu, Xiaolei Liu

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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

6 authors.

Long Nguyen Hoang DoLemole Center for Integrated Lymphatics and Vascular Research.
Jingjing PangLemole Center for Integrated Lymphatics and Vascular Research.ORCID 0000-0001-6228-2339
Esteban DelgadoLemole Center for Integrated Lymphatics and Vascular Research.
Liam FlynnLemole Center for Integrated Lymphatics and Vascular Research.ORCID 0009-0005-4709-4299
Hongxia LiuLemole Center for Integrated Lymphatics and Vascular Research.
Xiaolei LiuLemole Center for Integrated Lymphatics and Vascular Research.

Funding

Dissecting the functional roles of cardiac lymphatics in ischemic heart diseaseR01HL163269 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI XIAOLEI LIU · 2023 to 2026
$1.9M
NHLBI NIH HHS R01 HL163269
6 · The paper itself

Abstract

Background: Lymphatic valves are specialized structures within lymphatic vessels that ensure unidirectional lymph transport. Defective lymphatic valve formation is associated with lymphedema, a chronic disease characterized by impaired lymph drainage and the accumulation of protein-rich interstitial fluid. Lymphatic valves form during late embryonic stages in mice, with oscillatory shear stress implicated in regulating the molecular mechanisms which control lymphatic valve formation. However, the molecular mechanisms governing lymphatic valve formation remain incompletely understood. Although CXCR4 is regulated by shear stress in blood vessels, whether CXCL12/CXCR4 signaling regulates lymphatic valve formation and the underlying molecular mechanisms remain unknown. Methods: To investigate the roles of CXCR4 in the regulation of lymphatic valve development, we utilized lymphatic endothelial cell (LEC)-specific Results: LEC-specific loss of CXCR4 displayed impaired lymphatic valve development. Conclusions: Our findings reveal CXCL12/CXCR4 signaling acts as a critical regulator of lymphatic valve development. CXCL12/CXCR4 signaling integrates into the flow dependent AKT/FOXO1/FOXC2 signaling axis to coordinate lymphatic valve development and morphogenesis. Taken together, our study uncovers a previously unknown role of CXCL12/CXCR4 signaling pathway in the regulation of lymphatic valve development. Targeting CXCL12/CXCR4/AKT/FOXO1 axis may represent a promising therapeutic strategy for improving lymphatic valve development to improve lymphatic function for the treatment of lymphedema.

Indexed as

AKT/FOXO1CXCL12/CXCR4lymphatic valvemechanotransduction

Identifiers

PMID42539123
PMCPMC13419763

What OpenQuestion holds

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Registered trials

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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.