CXCL14 is a natural inhibitor of the CXCL12–CXCR4 signaling axis

Tanegashima, Kosuke; Suzuki, Kenji; Nakayama, Yuki; Tsuji, Kohei; Shigenaga, Akira; Otaka, Akira; Hara, Takahiko

doi:10.1016/j.febslet.2013.04.046

Cited by 85 publications

(107 citation statements)

References 26 publications

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“…MSCs secrete anti‐inflammatory, immunosuppressive, anti‐apoptotic and proangiogenic factors 29, 30. MSC‐conditioned medium increases capillary density and preserves cardiac function 31. Recent clinical trials have suggested that secretion of paracrine factors may be the underlying mechanism responsible for the improvement in outcomes 4.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Wang

et al. 2017

J Cellular Molecular Medi

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Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF‐1α, Tβ4, VEGF and SDF‐1 expression and decreased CXCL14 expression in hypoxic and serum‐deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF‐1α, Tβ4, VEGF, SDF‐1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial‐derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c‐kit+ cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c‐kit+ cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Wang

et al. 2017

J Cellular Molecular Medi

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“…CXCR3 has been demonstrated to bind to the ELR -CXC chemokines CXCL4, 9, 10 and 11 (21); however, it is unknown whether CXCR3 is the putative receptor for the ELR -chemokine-mediated inhibition of angiogenesis. CXCR4 is able to bind to CXCL12 and CXCL14 (22,23). As presented in Table I, CXCR7 has been identified as a further receptor for CXCL12 and CXCL11 (24).…”

Section: Features Of CXC Chemokines and Their Receptorsmentioning

confidence: 99%

Association between preeclampsia and the CXC chemokine family (Review)

Liu

Dai

Zhou

2015

Experimental and Therapeutic Medicine

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Abstract. Preeclampsia is a major cause of maternal and perinatal mortality and morbidity, characterized by gestational hypertension, proteinuria, systemic endothelial cell activation and an exaggerated inflammatory response. The precise cause of preeclampsia is not currently known; however, it is widely accepted that the pathogenesis of preeclampsia involves inadequate trophoblast invasion, leading to generalized endothelial dysfunction and an exaggerated inflammatory response. Chemokines are a superfamily of structurally similar proteins that mediate cell recruitment, angiogenesis, immunity and stem cell trafficking. CXC chemokines are a family of cytokines, unique in their ability to behave in a disparate manner in the regulation of angiogenesis. The CXC chemokine family further divides into two subfamilies; CXC ELR+, which promotes angiogenesis, and CXC ELR-, which inhibits angiogenesis. Furthermore, CXC chemokines are involved in the pathogenesis of various conditions, including malignant tumors, wound repair, chronic inflammation, atherosclerosis and potentially preeclampsia.

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“…Along with CCR5, it serves as one of the principal coreceptors for HIV entry into leukocytes (3), and is one of the most important chemokine receptors involved in cancer metastasis (4). Stromal-cell derived factor 1 (SDF-1 or CXCL12) was its only known ligand until recently, when CXCR4 was also shown to bind CXCL14 (5) and extracellular ubiquitin (6). Although structures of CXCR4 (7) and CCR5 (8) have been solved with synthetic antagonists, the structural basis for the interaction of CXCR4 (or any other chemokine receptor) with their natural ligands has yet to be determined.…”

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confidence: 99%

Stoichiometry and geometry of the CXC chemokine receptor 4 complex with CXC ligand 12: Molecular modeling and experimental validation

Kufareva

Stephens

Holden

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

124

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Chemokines and their receptors regulate cell migration during development, immune system function, and in inflammatory diseases, making them important therapeutic targets. Nevertheless, the structural basis of receptor:chemokine interaction is poorly understood. Adding to the complexity of the problem is the persistently dimeric behavior of receptors observed in cell-based studies, which in combination with structural and mutagenesis data, suggest several possibilities for receptor:chemokine complex stoichiometry. In this study, a combination of computational, functional, and biophysical approaches was used to elucidate the stoichiometry and geometry of the interaction between the CXC-type chemokine receptor 4 (CXCR4) and its ligand CXCL12. First, relevance and feasibility of a 2:1 stoichiometry hypothesis was probed using functional complementation experiments with multiple pairs of complementary nonfunctional CXCR4 mutants. Next, the importance of dimers of WT CXCR4 was explored using the strategy of dimer dilution, where WT receptor dimerization is disrupted by increasing expression of nonfunctional CXCR4 mutants. The results of these experiments were supportive of a 1:1 stoichiometry, although the latter could not simultaneously reconcile existing structural and mutagenesis data. To resolve the contradiction, cysteine trapping experiments were used to derive residue proximity constraints that enabled construction of a validated 1:1 receptor: chemokine model, consistent with the paradigmatic two-site hypothesis of receptor activation. The observation of a 1:1 stoichiometry is in line with accumulating evidence supporting monomers as minimal functional units of G protein-coupled receptors, and suggests transmission of conformational changes across the dimer interface as the most probable mechanism of altered signaling by receptor heterodimers.chemokine receptor | GPCR dimerization | molecular docking | functional complementation | cysteine trapping T he chemokine receptor CXCR4 regulates cell migration during many developmental processes (1, 2). Along with CCR5, it serves as one of the principal coreceptors for HIV entry into leukocytes (3), and is one of the most important chemokine receptors involved in cancer metastasis (4). Stromal-cell derived factor 1 (SDF-1 or CXCL12) was its only known ligand until recently, when CXCR4 was also shown to bind CXCL14 (5) and extracellular ubiquitin (6). Although structures of CXCR4 (7) and CCR5 (8) have been solved with synthetic antagonists, the structural basis for the interaction of CXCR4 (or any other chemokine receptor) with their natural ligands has yet to be determined. Numerous mutagenesis and NMR studies indicate that receptor:chemokine interactions involve two distinct sites (9-12), which has led to a two-site hypothesis of receptor activation (13). The so-called chemokine recognition site 1 (CRS1) (14) includes the N terminus of the receptor interacting with the globular core of the chemokine, whereas chemokine recognition site 2 (CRS2), located within the tra...

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CXCL14 is a natural inhibitor of the CXCL12–CXCR4 signaling axis

Cited by 85 publications

References 26 publications

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Association between preeclampsia and the CXC chemokine family (Review)

Stoichiometry and geometry of the CXC chemokine receptor 4 complex with CXC ligand 12: Molecular modeling and experimental validation

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