Mutual regulation of hypoxic and retinoic acid related signalling in tubular proximal cells

Fernández‐Martínez, Ana B.; Jiménez, María Isabel Arenas; Hernández, Irene Sánchez; García‐Bermejo, Maria Laura; Manzano, Victoria Moreno; Fraile, E; Lucio-Cazaña, Javier

doi:10.1016/j.biocel.2011.04.013

Cited by 24 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, KSHV infection and LANA, a KSHV-encoded latent gene, have been shown to induce the up-regulation of HIF [16] and at least one HIF-responsive gene (VEGFR1) in newly infected endothelial cells [23]. Also, several HIF-responsive genes related to angiogenesis or metabolism have been shown to be elevated in immortalized HUVECs chronically infected with KSHV [70]. However, these data do not provide a complete picture of the cellular response to KSHV infection and the role that hypoxia plays.…”

Section: Discussionmentioning

confidence: 99%

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

et al. 2017

View full text Add to dashboard Cite

Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression. We found that the gene expression signatures for KSHV infection and hypoxia have a 34% overlap. Moreover, there were considerable similarities between the genes up-regulated by hypoxia in uninfected (SLK) and in KSHV-infected (SLKK) cells. hsa-miR-210, a HIF-target known to have pro-angiogenic and anti-apoptotic properties, was significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Interestingly, expression of KSHV-encoded miRNAs was not affected by hypoxia. These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and that a substantial portion of hypoxia-induced changes in cellular gene expression are induced by KSHV infection. Therefore, targeting hypoxic pathways may be a useful way to develop therapeutic strategies for KSHV-related diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, Vegfa promoter does not have a RARE sequence and thus RA may not act directly to regulate Vegfa transcription (Liang et al 2013). HIF1A is the most potent transcriptional regulator of VEGFA (Pagès and Pouysségur, 2005) and RA has been shown to up regulate HIF1A in several cell types (Fernández-Martínez et al, 2012; Fernández-Martínez et al, 2011; Liang et al, 2014) Also, RARE sequences have been identified in the HIF1A promoter (Fernandez-Martinez et al 2012). Future work will address the exact mechanism through which meningeal-derived RA regulates VEGF-A in the developing cerebral cortex.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…Therefore, oxygen tension may control the immediate response after injury. Furthermore, oxygen tension is closely associated with the RA and TGF-β1 signalling pathways under physical and pathological conditions 49,50 . In this respect, we attempted to understand the process of prompt meningeal reconstruction in terms of the relationship between oxygen tension and the balance of RA and TGF-β1 signalling.…”

Section: Discussionmentioning

confidence: 99%

Prompt meningeal reconstruction mediated by oxygen-sensitive AKAP12 scaffolding protein after central nervous system injury

Wee

Seo

et al. 2014

Nat Commun

View full text Add to dashboard Cite

The meninges forms a critical epithelial barrier, which protects the central nervous system (CNS), and therefore its prompt reconstruction after CNS injury is essential for reducing neuronal damage. Meningeal cells migrate into the lesion site after undergoing an epithelial-mesenchymal transition (EMT) and repair the impaired meninges. However, the molecular mechanisms of meningeal EMT remain largely undefined. Here we show that TGF-β1 and retinoic acid (RA) released from the meninges, together with oxygen tension, could constitute the mechanism for rapid meningeal reconstruction. AKAP12 is an effector of this mechanism, and its expression in meningeal cells is regulated by integrated upstream signals composed of TGF-β1, RA and oxygen tension. Functionally, AKAP12 modulates meningeal EMT by regulating the TGF-β1-non-Smad-SNAI1 signalling pathway. Collectively, TGF-β1, RA and oxygen tension can modulate the dynamic change in AKAP12 expression, causing prompt meningeal reconstruction after CNS injury by regulating the transition between the epithelial and mesenchymal states of meningeal cells.

show abstract

Mutual regulation of hypoxic and retinoic acid related signalling in tubular proximal cells

Cited by 24 publications

References 35 publications

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

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

Prompt meningeal reconstruction mediated by oxygen-sensitive AKAP12 scaffolding protein after central nervous system injury

Contact Info

Product

Resources

About