Annexin A3 is necessary for parallel artery‐vein alignment in the mouse retina

Huang, Kexuan; Crist, Angela M.; Patel, Nehal; Blanks, Avery E.; Carter, Kelsey; Cleaver, Ondine; Meadows, Stryder M.

doi:10.1002/dvdy.154

Cited by 10 publications

(5 citation statements)

References 47 publications

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“…We also demonstrate that the ECM of the TAV patients was strongly enriched with Annexin A3 in comparison with that in the BAV patients. The biological function of Annexin A3 is largely unknown [ 42 ]. Other Annexins, but not Annexin A3, have been shown to be involved in the development of atherosclerosis [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies

Beusch,

Simonson,

Wedin

et al. 2023

Cell. Mol. Life Sci.

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Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV), quantified more than 1400 proteins per ECM sample by mass spectrometry, and demonstrated that local ECM preserves molecular cues of the pathophysiological processes. The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2. The abnormal physical stress on BAV may cause a mechanical injury leading to a continuous Tenascin C-driven presence of myofibroblasts and persistent fibrosis. The TAV ECM exhibited enrichment with Annexin A3 (p = 1.1 × 10–16 and the fold change 6.5) and a significant deficit in proteins involved in high-density lipid metabolism. These results were validated by orthogonal methods. The difference in the ECM landscape suggests distinct aetiologies between AVD of BAV and TAV; warrants different treatments of the patients with BAV and TAV; elucidates the molecular basis of AVD; and implies possible new therapeutic approaches. Our publicly available database (human_avd_ecm.surgsci.uu.se) is a rich source for medical doctors and researchers who are interested in AVD or heart ECM in general. Systematic proteomic analysis of local ECM using the methods described here may facilitate future studies of various tissues and organs in development and disease.

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Section: Discussionmentioning

confidence: 99%

Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies

Beusch,

Simonson,

Wedin

et al. 2023

Cell. Mol. Life Sci.

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“…In addition, Anxa5 interacts with Dectin-1, thereby facilitating apoptotic cell phagocytosis by dendritic cells that, in turn, can lead to peripheral tolerance to self-antigens [ 91 ]. The last of the upregulated annexin genes, Anxa3, is present in many organ systems and cell types, active in membrane and ion transport, cell signaling, endothelial migration, adipocyte differentiation and inflammation [ 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. While elevated Anxa3 levels have been shown to suppress apoptosis and autophagy through suppression of PKCδ-p38Mapk, depletion of Anxa3 apparently inhibits HIF1a-VEGF-dependent cell signaling [ 99 ].…”

Section: Discussionmentioning

confidence: 99%

A Temporal Comparative RNA Transcriptome Profile of the Annexin Gene Family in the Salivary versus Lacrimal Glands of the Sjögren’s Syndrome-Susceptible C57BL/6.NOD-Aec1Aec2 Mouse

Peck

Ambrus

2022

IJMS

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A generally accepted hypothesis for the initial activation of an immune or autoimmune response argues that alarmins are released from injured, dying and/or activated immune cells, and these products complex with receptors that activate signal transduction pathways and recruit immune cells to the site of injury where the recruited cells are stimulated to initiate immune and/or cellular repair responses. While there are multiple diverse families of alarmins such as interleukins (IL), heat-shock proteins (HSP), Toll-like receptors (TLR), plus individual molecular entities such as Galectin-3, Calreticulin, Thymosin, alpha-Defensin-1, RAGE, and Interferon-1, one phylogenetically conserved family are the Annexin proteins known to promote an extensive range of biomolecular and cellular products that can directly and indirectly regulate inflammation and immune activities. For the present report, we examined the temporal expression profiles of the 12 mammalian annexin genes (Anxa1-11 and Anxa13), applying our temporal genome-wide transcriptome analyses of ex vivo salivary and lacrimal glands from our C57BL/6.NOD-Aec1Aec2 mouse model of Sjögren’s Syndrome (SS), a human autoimmune disease characterized primarily by severe dry mouth and dry eye symptoms. Results indicate that annexin genes Anax1-7 and -11 exhibited upregulated expressions and the initial timing for these upregulations occurred as early as 8 weeks of age and prior to any covert signs of a SS-like disease. While the profiles of the two glands were similar, they were not identical, suggesting the possibility that the SS-like disease may not be uniform in the two glands. Nevertheless, this early pre-clinical and concomitant upregulated expression of this specific set of alarmins within the immune-targeted organs represents a potential target for identifying the pre-clinical stage in human SS as well, a fact that would clearly impact future interventions and therapeutic strategies.

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“…Littermate controls of both sexes were used in all experiments. Genotyping was performed as previously detailed 43 .…”

Section: Methodsmentioning

confidence: 99%

Endothelial Zmiz1 modulates physiological and pathophysiological angiogenesis during retinal development

Patel,

K C,

Chiang

et al. 2024

Preprint

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Angiogenesis is a highly coordinated process involving the control of various endothelial cell behaviors. Mechanisms for transcription factor involvement in the regulation of endothelial cell dynamics and angiogenesis have become better understood, however much remains unknown, especially the role of non-DNA binding transcriptional cofactors. Here, we show that Zmiz1, a transcription cofactor, is enriched in the endothelium and critical for embryonic vascular development, postnatal retinal angiogenesis, and pathological angiogenesis in oxygen induced retinopathy (OIR). In mice, endothelial cell-specific deletion ofZmiz1during embryogenesis led to lethality due to abnormal angiogenesis and vascular defects. Inducible endothelial cell-specific ablation ofZmiz1postnatally resulted in impaired retinal vascular outgrowth, decreased vascular density, and increased vessel regression. In addition, angiogenic sprouting in the superficial and deep layers of the retina was markedly reduced. Correspondingly, vascular sprouting in fibrin bead assays was significantly reduced in the absence of Zmiz1, while furtherin vitroandin vivoevidence also suggested deficits in EC migration. In agreement with the defective sprouting angiogenesis phenotype, gene expression analysis of isolated retinal endothelial cells revealed downregulation of tip-cell enriched genes upon inactivation ofZmiz1. Lastly, our study suggested that endothelial Zmiz1 is critical for intraretinal revascularization following hypoxia exposure in the OIR model. Taken together, these findings begin to define the previously unspecified role of endothelial Zmiz1 in physiological and pathological angiogenesis.

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Annexin A3 is necessary for parallel artery‐vein alignment in the mouse retina

Cited by 10 publications

References 47 publications

Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies

Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies

A Temporal Comparative RNA Transcriptome Profile of the Annexin Gene Family in the Salivary versus Lacrimal Glands of the Sjögren’s Syndrome-Susceptible C57BL/6.NOD-Aec1Aec2 Mouse

Endothelial Zmiz1 modulates physiological and pathophysiological angiogenesis during retinal development

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