ArticleMicrocirculation (New York, N.Y. : 1994)2025
AP-1 Is an Initial Convergent Transcriptional Response in Lymphatic Endothelium to VEGF-C or TNFα.
Article in Microcirculation (New York, N.Y. : 1994), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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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.
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.
Who cites it
1 citing paper in PubMed.
- Myeloid Activator Protein-1 Complex Contributes to Salt-Sensitive Hypertension.Circulation research · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
objectiveThe lymphatic vasculature plays a central role in resolving inflammation by draining interstitial fluid, immune cells, and inflammatory mediators. While vascular endothelial growth factor C (VEGF-C) is a well-established driver of lymphangiogenesis, the effects of chronic pro-inflammatory cytokines on lymphatic remodeling remain incompletely defined.
methodsHere, we investigated how tumor necrosis factor alpha (TNFα) compares with VEGF-C in regulating lymphatic endothelial structure and function using human dermal lymphatic endothelial cells (HDLECs).
resultsIn tube formation and spheroid sprouting assays, both VEGF-C and TNFα supported early lymphangiogenic events, promoting robust sprouting and network development within 24 h. However, when pre-formed microvascular networks were challenged, prolonged TNFα exposure triggered progressive destabilization, characterized by tube fragmentation, reduced proliferation, and impaired metabolic activity, whereas VEGF-C preserved network stability. Mechanistically, both VEGF-C and TNFα induced rapid phosphorylation of p38 MAPK and upregulation of Activator Protein-1 (AP-1) transcription factor subunits within 30 min, suggesting a convergent early transcriptional response. Bulk RNA-sequencing confirmed shared induction of AP-1 family genes (FOS, JUN, ATF), highlighting AP-1 as a candidate regulator of the transition between adaptive and maladaptive outcomes. We propose that transient AP-1 activation promotes pro-lymphangiogenic programs, while sustained TNFα signaling redirects AP-1 activity toward stress, growth arrest, and apoptosis, leading to lymphatic regression.
conclusionThese findings identify TNFα as a temporally bifunctional regulator of lymphatic endothelial fate.
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Registered trials
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.