Retinoic acid increases hypoxia-inducible factor-1α through intracrine prostaglandin E2 signaling in human renal proximal tubular cells HK-2

Fernández‐Martínez, Ana B.; Jiménez, María Isabel Arenas; Lucio-Cazaña, Javier

doi:10.1016/j.bbalip.2012.01.010

Cited by 21 publications

(20 citation statements)

References 45 publications

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“…Unlike results that occur in several other cells types (Ji et al, 2010; Fernandez-Martinez et al, 2012a; Fernandez-Martinez et al, 2012b), however, we found no increase in HIFα subunit expression by PGE 2 , although we did observe potent synergy between PGE 2 and hypoxia on HIF activity. This might occur through a PGE 2 dependent increase in HIFα activation that can occur independently of HIFα synthesis, as we reported for C/EBPδ and Runx2 (McCarthy et al, 2000c; Ji, 2003), but to our knowledge HIFα activation has not been previously addressed in this context.…”

Section: Discussioncontrasting

confidence: 99%

Stratified control of IGF-I expression by hypoxia and stress hormones in osteoblasts

McCarthy

Yun

Madri

et al. 2014

Gene

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Bone cells respond to the integrated effects of local and systemic regulation. Here we show that hypoxia and the stress hormones PGE2 and glucocorticoid interact in complex ways in osteoblasts, converging on insulin like growth factor I (IGF-I) expression. Whereas hypoxia alone rapidly increased transcription factor HIF activity, it suppressed DNA synthesis, had no significant effects on protein synthesis or alkaline phosphatase activity, and drove discrete changes in a panel of osteoblast mRNAs. Notably, hypoxia increased expression of the acute phase response transcription factors C/EBPδ which can induce IGF-I in response to PGE2, but conversely prevented the stimulatory effect of PGE2 on IGF-I mRNA. However, unlike its effect on C/EBPδ, hypoxia suppressed expression of the obligate osteoblast transcription factor Runx2, which can activate an upstream response element in the IGF-I gene promoter. Hypoxic inhibition of IGF-I and Runx2 were enforced by glucocorticoid, and continued with prolonged exposure. Our studies thus reveal that IGF-I expression is stratified by two critical transcriptional elements in osteoblasts, which are resolved by the individual and combined effects of hypoxic stress and stress hormones. In so doing, hypoxia suppresses Runx2, limits the enhancing influence of PGE2, and interacts with glucocorticoid to reduce IGF-I expression by osteoblasts.

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Section: Discussioncontrasting

confidence: 99%

Stratified control of IGF-I expression by hypoxia and stress hormones in osteoblasts

McCarthy

Yun

Madri

et al. 2014

Gene

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“…On the other hand, it was also reported that intracellular PGE 2 increased HIF-1α expression in human renal proximal tubular cells (HK2 cells). (48) Moreover, the study demonstrated that COX/PGE 2 mediated all-trans retinoic acid (ATRA) induced upregulation of HIF-1α in HK2 cells even in normoxia. Taken together, it seems that there is a crosstalk between HIF-1α and COX/PGE 2 pathway.…”

Section: Discussionmentioning

confidence: 99%

Regulation and function of renal medullary cyclooxygenase-2 during high salt loading

Yang

Liu

2017

Front Biosci

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Prostaglandins (PGs) are important autocrine/paracrine regulators that contribute to sodium balance and blood pressure control. Along the nephron, the highest amount of PGE2 is found in the distal nephron, an important site for fine-tuning of urinary sodium and water excretion. Cylooxygenase-2 (COX-2) is abundantly expressed in the renal medulla and its expression along with urinary PGE2 excretion is highly induced by chronic salt loading. Factors involved in high salt-induced COX-2 expression in the renal medulla include the hypertonicity, fluid shear stress (FSS), and hypoxia-inducible factor-1α (HIF-1 α). Site-specific inhibition of COX-2 in the renal medulla of Sprague-Dawley rats causes sodium retention and salt-sensitive hypertension. Together, these results support the concept that renal medullary COX-2 functions an important natriuretic mediator that is activated by salt loading and its products promote sodium excretion and contribute to maintenance of sodium balance and blood pressure.

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“…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

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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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Retinoic acid increases hypoxia-inducible factor-1α through intracrine prostaglandin E2 signaling in human renal proximal tubular cells HK-2

Cited by 21 publications

References 45 publications

Stratified control of IGF-I expression by hypoxia and stress hormones in osteoblasts

Stratified control of IGF-I expression by hypoxia and stress hormones in osteoblasts

Regulation and function of renal medullary cyclooxygenase-2 during high salt loading

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

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