<i>In vivo</i> synthesis and secretion of erythropoietin by genetically modified primary human keratinocytes grafted onto immunocompromised mice

Scheidemann, Frank; Therrien, Jean-Philippe; Vogel, Jon D.; Pfützner, Wolfgang

doi:10.1111/j.1600-0625.2009.00984.x

Cited by 4 publications

(1 citation statement)

References 77 publications

(105 reference statements)

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“…In monolayer cultures as well as in an in vitro multilayered skin model, however, transduced keratinocytes synthesized significantly more EPO than transduced fibroblasts, which correlated with increased vector incorporation in those EPO‐transduced keratinocytes . Furthermore this group was able to show that EPO‐transduced keratinocytes, which were grafted on mice, presented a stable EPO production over a 6‐month period …”

Section: Epo‐induced Effects In Physiological Wound Healing Of the Skinmentioning

confidence: 99%

The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

Sorg

Harder

Krueger

et al. 2012

Medicinal Research Reviews

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Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.

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Section: Epo‐induced Effects In Physiological Wound Healing Of the Skinmentioning

confidence: 99%

The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

Sorg

Harder

Krueger

et al. 2012

Medicinal Research Reviews

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Erythropoietin gene doping: facts and fictions

Jelkmann¹

2012

Sportwiss

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Hypoxia-mediated control of HIF/ARNT machinery in epidermal keratinocytes

Weir

Robertson

Leigh

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Transcriptional activity of hypoxia-induced factor 1 (HIF1) - a heterodimer of HIF1α and ARNT (HIF1β) - is essential for cellular adaptation to environmental stress and plays an important role in skin development, wound healing, tumorigenesis and barrier function. Using primary mouse and human epidermal keratinocytes at ambient or hypoxic (1% O(2)) conditions we studied effects of hypoxia upon HIF protein expression. Significant nuclear levels of ARNT and HIF1α along with high HIF1 activity in normoxic keratinocytes suggest an as yet uncharacterised oxygen-independent role for HIF pathway in the epidermis. Acute hypoxia results in an instant but transient increase of HIF1α protein accompanied by a gradual decrease in its mRNA, while ARNT expression remains unchanged. In prolonged (chronic) hypoxia both HIF1α and Arnt are downregulated along with decline of HIF1 activity. However, expression of classical HIF1 targets such as Selenbp1 and Vegfa remains high. Thus, keratinocytes respond to acute hypoxia with immediate block of HIF1α protein degradation and concomitant increase of HIF activity, while under chronic hypoxia pro-angiogenic signalling is maintained through HIF1-independent pathway(s). Decline of HIF1α during chronic exposure is controlled at both mRNA and protein levels, while Arnt is downregulated post-translationally. Distinct transcription levels of Hif1α and Hif3α splice variants under normoxia and their differential response to hypoxia suggest functional diversity of Hif-α isoforms and highlight the complexity of HIF machinery control in epidermal keratinocytes.

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In vivo synthesis and secretion of erythropoietin by genetically modified primary human keratinocytes grafted onto immunocompromised mice

Cited by 4 publications

References 77 publications

The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

Erythropoietin gene doping: facts and fictions

Hypoxia-mediated control of HIF/ARNT machinery in epidermal keratinocytes

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