PUBLICATION
Disruption of Swell1/VRAC function impairs initial hemodynamics and activates compensatory leukotriene signaling in zebrafish circulation development
- Authors
- Tseng, Y.T., Chang, C.T., HuangFu, W.C., Liu, I.H.
- ID
- ZDB-PUB-260105-10
- Date
- 2025
- Source
- Frontiers in cell and developmental biology 13: 17195441719544 (Journal)
- Registered Authors
- Liu, I-Hsuan, Tseng, Yen-Tzu
- Keywords
- 5-lipoxygenase, LRRC8A, VRAC, Zebrafish, arachidonic acid metabolism, circulatory system development, swel1
- MeSH Terms
- none
- PubMed
- 41488008 Full text @ Front Cell Dev Biol
Citation
Tseng, Y.T., Chang, C.T., HuangFu, W.C., Liu, I.H. (2025) Disruption of Swell1/VRAC function impairs initial hemodynamics and activates compensatory leukotriene signaling in zebrafish circulation development. Frontiers in cell and developmental biology. 13:17195441719544.
Abstract
Background Volume-regulated anion channels (VRACs) maintain cell-volume homeostasis, and SWELL1 is their essential subunit. Here, we show that VRAC/Swell1 also regulates initial hemodynamics and vascular development in zebrafish.
Results Stable swell1a and swell1b mutant zebrafish lines were established. In SWELL1- KO HAP1 cells, VRAC currents were rescued by wild-type, but not mutant, zebrafish swell1a or swell1b cDNA, confirming the alleles' loss-of-function nature. Microangiography and Tg(fli1a:eGFP) imaging revealed hypovolemia, reduced flow, and delayed vessel sprouting by 30 hpf, with severity proportional to allele dosage and partial recovery by 72 hpf. Whole-embryo transcriptomics highlighted upregulation of arachidonic-acid metabolism, especially the 5- lipoxygenase (5LO) axis. Pharmacological 5LO inhibition or the receptor cyslt1r knockdown aggravated circulatory defects, whereas leukotriene C4 treatment improved hemodynamics, indicating compensatory 5LO signalling. Thus, Swell1-dependent VRAC activity underpins embryonic hemodynamic stability, and 5LO-derived mediators partially buffer its loss.
Conclusion These findings link ion-channel function to lipid signalling in vascular development and suggest VRAC/Swell1-5LO cross-talk as a therapeutic target for blood-flow disorders.
Errata / Notes
Corrected by: ZDB-PUB-260207-2
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