MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression

Aranda, Juan; Reglero-Real, Natalia; Marcos‐Ramiro, Beatriz; Ruiz-Sáenz, Ana; Fernández-Martín, Laura; Bernabé‐Rubio, Miguel; Kremer, Leonor; Ridley, Anne J.; Correas, Isabel; Alonso, Miguel A.; Millán, Jaime

doi:10.1091/mbc.e11-11-0914

Cited by 42 publications

(42 citation statements)

References 62 publications

(58 reference statements)

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“…Myelin-associated oligodendrocyte basic protein and myelin oligodendrocyte glycoprotein, two important myelin proteins in stabilizing the myelin sheath, showed no obvious alterations. Myeloid-associated differentiation marker (MYADM), which controls endothelial barrier function (Aranda et al 2013), was decreased in the HIP (81.2%) and HYP (89.1%) and increased in the PFC (141.0%) of the OVX rats (Fig. 3c).…”

Section: Resultsmentioning

confidence: 93%

“…MYADM controls endothelial barrier function (Aranda et al . ), and deficiency of Cavin‐1 induced dysfunction of the small arteries (Swärd et al . ).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, dysfunction of the endothelial barrier in the brain after OVX was suggested by decreased levels of MYADM in the HIP and HYP and decreased levels of Cavin-1 in the AMY. MYADM controls endothelial barrier function (Aranda et al 2013), and deficiency of Cavin-1 induced dysfunction of the small arteries (Sw€ ard et al 2014). In addition, increased csynuclein in the HYP (129.5%) and AMY (131.2%) were shown (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Evidence of altered depression and dementia‐related proteins in the brains of young rats after ovariectomy

Fang

Zeng

et al. 2018

Journal of Neurochemistry

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Menopause, a risk factor for brain dysfunction in women, is characterized by neuropsychological symptoms including depression and dementia, which are closely related to alterations in different brain regions after menopause. However, little is known about the variability in pathophysiologic changes associated with menopause in the brain. Here, we observed that menopause in rats induced by bilateral ovariectomy (OVX) showed depressive and dementia-related behaviors along with neuronal loss in the prefrontal cortex (PFC), hippocampus (HIP), hypothalamus (HYP), and amygdala (AMY) by Nissl staining. Meanwhile, by immunohistochemical staining, increased microglia in the HIP and AMY and increased astrocytes in the PFC, HYP, and AMY were shown. Using quantitative proteomics, we identified 146 differentially expressed proteins in the brains of OVX rats, for example, 20 in the PFC, 41 in the HIP, 17 in the HYP, and 79 in the AMY, and performed further detection by western blotting. A link between neuronal loss and apoptosis was suggested, as evidenced by increases in adenylate kinase 2 (AK2), B-cell lymphoma 2 associated X (Bax), cleaved caspase 3, and phosphorylated p53 and decreases in Huntingtin-interacting protein K, hexokinase, and phosphorylated B-cell lymphoma 2 (Bcl-2), and apoptosis might be triggered by endoplasmic reticulum stress (probed by increased glucose-regulated protein 78 (GRP78), cleaved caspase 12, phosphorylated protein kinase R (PKR)-like endoplasmic reticulum kinase, inositol-requiring enzyme-1 and activating transcription factor 6), and mitochondrial dysfunction (probed by increased cytochrome c and cleaved caspase 3 and decreased sideroflexin-1 (SFXN1) and NADH dehydrogenase (ubiquinone) 1 α subcomplex 11 (NDUFA11)). Activation of autophagy was also indicated by increased autophagy-related 7, γ-aminobutyric acid (GABA) receptor-associated protein-like 2, and oxysterol-binding protein-related protein 1 and confirmed by increased microtubule-associated protein light chain 3 (LC3II/I), autophagy-related 5, and Beclin1 in the HIP and AMY. In the AMY, which is important in emotion, higher GABA transporter 3 and lower vesicular glutamate transporter 1 levels indicated an imbalance between excitatory and inhibitory neurotransmission, and the increased calretinin and decreased calbindin levels suggested an adjustment of GABAergic transmission after OVX. In addition, cytoskeletal abnormalities including tau hyperphosphorylation, dysregulated Ca² signals, and glutamic synaptic impairments were observed in the brains of OVX rats. Collectively, our study showed the changes in different brain regions related to depression and dementia during menopause.

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Section: Resultsmentioning

confidence: 93%

“…MYADM controls endothelial barrier function (Aranda et al . ), and deficiency of Cavin‐1 induced dysfunction of the small arteries (Swärd et al . ).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evidence of altered depression and dementia‐related proteins in the brains of young rats after ovariectomy

Fang

Zeng

et al. 2018

Journal of Neurochemistry

View full text Add to dashboard Cite

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“…5, K and L), including genes implicated in regulation of cell-matrix interactions ( Lgals1 , Fxyd5 ), metabolism ( Bola2, Echs, Eno1 , Gcsh ), and myeloid differentiation of HSPCs ( Myadm ). Myadm has recently been shown to regulate endothelial inflammation (Aranda et al, 2013), and increased expression of Myadm was observed in mesenchymal stromal cells derived from patients with myeloproliferative neoplasms (Ramos et al, 2017). Since inflammation-associated aging or “inflammaging” has recently emerged as a critical process driving HSPC aging phenotypes, it is likely that genes regulating endothelial inflammation may impact HSPC aging (Kovtonyuk et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Endothelial mTOR maintains hematopoiesis during aging

Ramalingam

Poulos

Gutkin

et al. 2020

Journal of Experimental Medicine

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Aging leads to a decline in hematopoietic stem and progenitor cell (HSPC) function. We recently discovered that aging of bone marrow endothelial cells (BMECs) leads to an altered crosstalk between the BMEC niche and HSPCs, which instructs young HSPCs to behave as aged HSPCs. Here, we demonstrate aging leads to a decrease in mTOR signaling within BMECs that potentially underlies the age-related impairment of their niche activity. Our findings reveal that pharmacological inhibition of mTOR using Rapamycin has deleterious effects on hematopoiesis. To formally determine whether endothelial-specific inhibition of mTOR can influence hematopoietic aging, we conditionally deleted mTOR in ECs (mTOR(ECKO)) of young mice and observed that their HSPCs displayed attributes of an aged hematopoietic system. Transcriptional profiling of HSPCs from mTOR(ECKO) mice revealed that their transcriptome resembled aged HSPCs. Notably, during serial transplantations, exposure of wild-type HSPCs to an mTOR(ECKO) microenvironment was sufficient to recapitulate aging-associated phenotypes, confirming the instructive role of EC-derived signals in governing HSPC aging.

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“…Further analysis of our transcriptome data set revealed 13 such genes (Figure 5K-L), including genes implicated in regulation of cell-matrix interactions (Lgals1, Fxyd5), metabolism (Bola2, Echs, Eno1, Gcsh) and myeloid differentiation of HSPCs (Myadm). Myadm has recently been shown to regulate endothelial inflammation (Aranda et al, 2013) and increased expression of Myadm was observed in mesenchymal stromal cells (MSCs) derived from patients of myeloproliferative neoplasms (Ramos et al, 2017). Since inflammation-associated aging or 'inflammaging' has recently emerged as a critical process driving HSPC aging phenotypes, it is likely that genes regulating endothelial inflammation might impact HSPC aging (Kovtonyuk et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Endothelial mTOR maintains hematopoiesis during aging

Ramalingam

Poulos

Gutkin

et al. 2020

Preprint

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AbstractAging leads to a decline in hematopoietic stem and progenitor cell (HSPC) function. We recently discovered that aging of bone marrow endothelial cells (BMECs) leads to an altered crosstalk between the BMEC niche and HSPCs, that instructs young HSPCs to behave as aged HSPCs. Here, we demonstrate aging leads to a decrease in mTOR signaling within BMECs that potentially underlies the age-related impairment of their niche activity. Our findings reveal that pharmacological inhibition of mTOR using Rapamycin has deleterious effects on hematopoiesis. To formally determine whether endothelial-specific inhibition of mTOR can influence hematopoietic aging, we conditionally deleted mTOR in ECs (mTOR(ECKO)) of young mice and observed that their HSPCs displayed attributes of an aged hematopoietic system. Transcriptional profiling of HSPCs from mTOR(ECKO) mice revealed that their transcriptome resembled aged HSPCs. Notably, during serial transplantations, exposure of wild type HSPCs to an mTOR(ECKO) microenvironment was sufficient to recapitulate aging-associated phenotypes, confirming the instructive role of EC-derived signals in governing HSPC aging.SummaryRamalingam et al. demonstrate that pharmacological inhibition of mTOR adversely impacts aging hematopoiesis. The authors demonstrate that aging results in decreased mTOR signaling within the bone marrow endothelium and endothelial-specific inhibition of mTOR causes hematopoietic defects observed during physiological aging.

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MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression

Cited by 42 publications

References 62 publications

Evidence of altered depression and dementia‐related proteins in the brains of young rats after ovariectomy

Evidence of altered depression and dementia‐related proteins in the brains of young rats after ovariectomy

Endothelial mTOR maintains hematopoiesis during aging

Endothelial mTOR maintains hematopoiesis during aging

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