ArticleJCI insight2024
Connexin-45 is expressed in mouse lymphatic endothelium and required for lymphatic valve function.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026Review
- The Thoracic Lymphatic Vasculature: Interorgan Strategies to Achieve an Optimal Tissue Function.Comprehensive Physiology · 2026Review
- PROX1-associated lymphatic reprogramming signatures in pediatric adamantinomatous craniopharyngioma: a comparative study with adult cases.Frontiers in pediatrics · 2026Article
- Venous Tone is a Critical Determinant of Venous Valve Closure in the Mouse.Function (Oxford, England) · 2025Article
- Hierarchical Requirement for Endothelial Cell Connexins Cx37, Cx47, Cx43, and Cx45 in Lymphatic Valve Function.Function (Oxford, England) · 2025Article
- Identification of GJC1 as a novel diagnostic marker for papillary thyroid carcinoma using weighted gene co-expression network analysis and machine learning algorithm.Discover oncology · 2025Article
- Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.Frontiers in cell and developmental biology · 2025Review
- The ion transport, GPCR, and RTK toolkit expression in the human cerebrovascular endothelial cell line, hCMEC/D3: an Omics perspective.Frontiers in physiology · 2025Article
- Developmental progression of lymphatic valve morphology and function.Frontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The expression and functional relevance of the gap junction molecule connexin-45 (Cx45; GJC1) in lymphatic endothelium were not previously known. We found that Cx45 was expressed widely in the endothelium of murine lymphatics, in both valve and nonvalve regions. Cell-specific deletion of Cx45, driven by a constitutive Cre line (Lyve1-Cre) or an inducible Cre line (Prox1-CreERT2), compromised the function of lymphatic valves, as assessed by physiological tests (back leak and closure) of isolated, single-valve vessel segments. The defects were comparable to those previously reported for loss of Cx43, and as with Cx43, deletion of Cx45 resulted in shortening or increased asymmetry of lymphatic valve leaflets, providing an explanation for the compromised valve function. In contrast with Cx43, lymphatic endothelial cell-specific (LEC-specific) deletion of Cx45 did not alter the number of valves in mesenteric or dermal lymphatic networks or the expression patterns of the canonical valve-associated proteins PROX1, ITGA9, or CLAUDIN5. Constitutive deletion of Cx45 from LECs resulted in increased backflow of injected tracer in popliteal networks in vivo and compromised the integrity of the LEC permeability barrier in a subset of collecting vessels. These findings provide evidence for an unexpected role of Cx45 in the development and maintenance of lymphatic valves.
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