Retinoic acid stimulation of VEGF secretion from human endometrial stromal cells is mediated by production of reactive oxygen species

Wu, Juanjuan; Hansen, Jason M.; Hao, Lijuan; Taylor, Robert N.; Sidell, Neil

doi:10.1113/jphysiol.2010.200808

Cited by 16 publications

(8 citation statements)

References 66 publications

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“…Although it remains controversial whether beige adipocytes are generated by de novo adipogenesis or conversion of existing adipocytes ( Rosenwald et al, 2013 , Wang et al, 2013 ), progenitor cells on endothelial vessels are capable to differentiate into beige adipocytes ( Tran et al, 2012 , Min et al, 2016 , Vishvanath et al, 2016 ). Obesity and diabetes impair the angiogenic potential of adipose tissue stem cells ( Rennert et al, 2014 , Togliatto et al, 2016 ), and stimulation of angiogenesis via Vegfa over-expression promotes adipose tissue thermogenesis and protects against diet-induced obesity ( Wu et al, 2011 , Sun et al, 2014a ). Thus, enhancing angiogenesis is an effective strategy to promote beige adipogenesis in adipose tissue impaired due to obesity and diabetes.…”

Section: Discussionmentioning

confidence: 99%

Maternal Retinoids Increase PDGFRα+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development

Wang

Liang

et al. 2017

EBioMedicine

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Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα+ adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA. Furthermore, RA-induced beige adipogenesis was blocked following vascular endothelial growth factor receptor (VEGFR) 2 knock out in PDGFRα+ cells, suggesting its mediatory role. Our data reveal an intrinsic link between maternal retinoid level and offspring health via promoting beige adipogenesis. Thus, enhancing maternal retinoids is an amiable therapeutic strategy to prevent obesity in offspring, especially for those born to obese mothers which account for one third of all pregnancies.

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Section: Discussionmentioning

confidence: 99%

Maternal Retinoids Increase PDGFRα+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development

Wang

Liang

et al. 2017

EBioMedicine

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“…9). RA has been shown to upregulate expression of VEGF-A in several cell culture model systems (Liang et al, 2013, 2014; Wu et al, 2011). RA stimulates signaling in target cells through its receptors, RAR and RXR, which bind to DNA motifs known as retinoic acid response elements (RARE), in the promoter of the target genes (Ruberte et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular defects in Foxc1 mutants correlate with aberrant WNT and VEGF—A pathways downstream of retinoic acid from the meninges

Mishra

Choe

Pleasure

et al. 2016

Developmental Biology

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Growth and maturation of the cerebrovasculature is a vital event in neocortical development however mechanisms that control cerebrovascular development remain poorly understood. Mutations in or deletions that include the FOXC1 gene are associated with congenital cerebrovascular anomalies and increased stroke risk in patients. Foxc1 mutant mice display severe cerebrovascular hemorrhage at late gestational ages. While these data demonstrate Foxc1 is required for cerebrovascular development, its broad expression in the brain vasculature combined with Foxc1 mutant’s complex developmental defects have made it difficult to pinpoint its function(s). Using global and conditional Foxc1 mutants, we find 1) significant cerebrovascular growth defects precede cerebral hemorrhage and 2) expression of Foxc1 in neural crest-derived meninges and brain pericytes, though not endothelial cells, is required for normal cerebrovascular development. We provide evidence that reduced levels of meninges-derived retinoic acid (RA), caused by defects in meninges formation in Foxc1 mutants, is a major contributing factor to the cerebrovascular growth defects in Foxc1 mutants. We provide data that suggests that meninges-derived RA ensures adequate growth of the neocortical vasculature via regulating expression of WNT pathway proteins and neural progenitor derived-VEGF-A. Our findings offer the first evidence for a role of the meninges in brain vascular development and provide new insight into potential causes of cerebrovascular defects in patients with FOXC1 mutations.

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“…Moreover, both human endothelial cells and osteoblasts increased VEGFA mRNA expression when exposed to RA. In fact, we previously identified elevated Vegfa (and Cyp26b1 ) levels in bone tissue of rats with hypervitaminosis A, using microarray analysis ( Lind et al, 2012 ) and earlier studies show increased production/release of Vegfa from mouse osteoblasts and other cell types/tissues upon RA treatment ( Harada et al, 1994 ; Maeno et al, 2002 ; Tanabe et al, 2004 ; Wu et al, 2011 ; Tan et al, 2015 ). The rapid normalization in plasma Vegfa after two days of excess vitamin A ingestion, might be explained by the powerful feedback mechanisms (involving Cyp26b1) that exist in vivo for reducing harmful effects of excess vitamin A ( Lee et al, 2012 ).…”

Section: Discussionmentioning

confidence: 90%

Bones in human CYP26B1 deficiency and rats with hypervitaminosis A phenocopy Vegfa overexpression

et al. 2018

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Angulated femurs are present prenatally both in CYP26B1 deficient humans with a reduced capacity to degrade retinoic acid (RA, the active metabolite of vitamin A), and mice overexpressing vascular endothelial growth factor a (Vegfa). Since excessive ingestion of vitamin A is known to induce spontaneous fractures and as the Vegfa-induced femur angulation in mice appears to be caused by intrauterine fractures, we analyzed bones from a CYP26B1 deficient human and rats with hypervitaminosis A to further explore Vegfa as a mechanistic link for the effect of vitamin A on bone. We show that bone from a human with CYP26B1 mutations displayed periosteal osteoclasts in piles within deep resorption pits, a pathognomonic sign of hypervitaminosis A. Analysis of the human angulated fetal femur revealed excessive bone formation in the marrow cavity and abundant blood vessels. Normal human endothelial cells showed disturbed cell-cell junctions and increased CYP26B1 and VEGFA expression upon RA exposure. Studies in rats showed increased plasma and tissue Vegfa concentrations and signs of bone marrow microhemorrhage on the first day of excess dietary vitamin A intake. Subsequently hypervitaminosis A rats displayed excess bone formation, fibrosis and an increased number of megakaryocytes in the bone marrow, which are known characteristics of Vegfa overexpression. This study supports the notion that the skeletal phenotype in CYP26B1 deficient human bone is caused by excess RA. Our findings suggest that an initial part of the vitamin A mechanism causing bone alterations is mediated by excess Vegfa and disturbed bone marrow microvessel integrity.

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Retinoic acid stimulation of VEGF secretion from human endometrial stromal cells is mediated by production of reactive oxygen species

Cited by 16 publications

References 66 publications

Maternal Retinoids Increase PDGFRα+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development

Maternal Retinoids Increase PDGFRα+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development

Cerebrovascular defects in Foxc1 mutants correlate with aberrant WNT and VEGF—A pathways downstream of retinoic acid from the meninges

Bones in human CYP26B1 deficiency and rats with hypervitaminosis A phenocopy Vegfa overexpression

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