Hypoxia pathway proteins regulate the synthesis and release of epinephrine in the mouse adrenal gland

Watts, Deepika; Bechmann, Nicole; Meneses, Ana; Poutakidou, Ioanna K.; Kaden, Denise; Conrad, Catleen; Krueger, A. P.; Stein, Johanna; El‐Armouche, Ali; Chavakis, Triantafyllos; Eisenhofer, Graeme; Peitzsch, Mirko; Wielockx, Ben

doi:10.1101/2020.10.15.340943

Cited by 2 publications

(1 citation statement)

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“…During birth, increased catecholamine release facilitates adequate hemodynamic adjustment and stimulates surfactant production by the lungs (73, 74). A deficiency of Phd2 in the adrenal medulla of mice results in a Hif2a-mediated reduction in phenylethanolamine N-methyltransferase (Pnmt) associated with a reduced epinephrine biosynthesis (75). This is also consistent with studies in Hif2a -/mice, which showed reduced epinephrine levels in the adrenal gland (68,76).…”

Section: Hif Signaling During Neural Crest and Adrenal Developmentsupporting

confidence: 72%

HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics

Bechmann¹,

Westermann²,

Eisenhofer³

2023

Front. Endocrinol.

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Pediatric neural crest-derived adrenal neoplasms include neuroblastoma and pheochromocytoma. Both entities are associated with a high degree of clinical heterogeneity, varying from spontaneous regression to malignant disease with poor outcome. Increased expression and stabilization of HIF2α appears to contribute to a more aggressive and undifferentiated phenotype in both adrenal neoplasms, whereas MYCN amplification is a valuable prognostic marker in neuroblastoma. The present review focuses on HIF- and MYC signaling in both neoplasms and discusses the interaction of associated pathways during neural crest and adrenal development as well as potential consequences on tumorigenesis. Emerging single-cell methods together with epigenetic and transcriptomic analyses provide further insights into the importance of a tight regulation of HIF and MYC signaling pathways during adrenal development and tumorigenesis. In this context, increased attention to HIF-MYC/MAX interactions may also provide new therapeutic options for these pediatric adrenal neoplasms.

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Section: Hif Signaling During Neural Crest and Adrenal Developmentsupporting

confidence: 72%

HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics

Bechmann¹,

Westermann²,

Eisenhofer³

2023

Front. Endocrinol.

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HIF2α is a direct regulator of neutrophil motility

Sormendi

Deygas

Sinha

et al. 2021

Blood

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Orchestrated recruitment of neutrophils to inflamed tissue is essential during initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it is still unclear how these factors influence the migration of neutrophils to and at the site of inflammation either during their transmigration through the blood-endothelial cell barrier, or their motility in the interstitial space. Here, we reveal that activation of the Hypoxia Inducible Factor-2 (HIF2α) due to deficiency of HIF-prolyl hydroxylase domain protein-2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments. In vivo, the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in models of acute local inflammation. Using systematic RNAseq analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2α-dependent neutrophil motility. Thus, we propose that the here identified novel PHD2-HIF2α-RhoA axis is vital to the initial stages of inflammation as it promotes neutrophil movement through highly confined tissue landscapes.

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Hypoxia pathway proteins regulate the synthesis and release of epinephrine in the mouse adrenal gland

Cited by 2 publications

References 57 publications

HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics

HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics

HIF2α is a direct regulator of neutrophil motility

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