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Título:
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Increased hypoxic proliferative response and gene expression in erythroid progenitor cells of Andean highlanders with Chronic Mountain Sickness.
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Autores:
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Bermudez, Daniela ;
Azad, Priti ;
Figueroa-Mujíca, Rómulo ;
Vizcardo-Galindo, Gustavo ;
Corante, Noemi ;
Guerra-Giraldez, Cristina ;
Haddad, Gabriel G. ;
Villafuerte, Francisco C.
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Tipo de documento:
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texto impreso
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Editorial:
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American Physiological Society, 2019-12-06T20:57:40Z
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Nota general:
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info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
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Idiomas:
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Inglés
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Palabras clave:
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Editados por otras instituciones
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Artículos
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Artículos en revistas indizadas
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Resumen:
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Excessive erythrocytosis (EE) is the main sign of Chronic Mountain Sickness (CMS), a maladaptive clinical syndrome prevalent in Andean and other high-altitude populations worldwide. The pathophysiological mechanism of EE is still controversial, as physiological variability of systemic respiratory, cardiovascular, and hormonal responses to chronic hypoxemia complicates the identification of underlying causes. Induced pluripotent stem cells derived from CMS highlanders showed increased expression of genes relevant to the regulation of erythropoiesis, angiogenesis, cardiovascular, and steroid-hormone function that appear to explain the exaggerated erythropoietic response. However, the cellular response to hypoxia in native CMS cells is yet unknown. This study had three related aims: to determine the hypoxic proliferation of native erythroid progenitor BFU-E cells derived from CMS and non-CMS peripheral blood mononuclear cells; to examine their SENP1, GATA1, EPOR, and EPO expression; and to investigate the functional upstream role of SENP1 in native progenitor differentiation into erythroid precursors. Native CMS BFU-E colonies showed increased proliferation under hypoxic conditions compared to non-CMS cells, together with an up-regulated expression of SENP1, GATA1, EPOR; and no difference in EPO expression. Knock-down of the SENP1 gene abolished the augmented proliferative response. Thus, we demonstrate that native CMS progenitor cells produce a larger proportion of erythroid precursors under hypoxia and that SENP1 is essential for proliferation. Our findings suggest a significant intrinsic component for developing EE in CMS highlanders at the cellular and gene expression level that could be further enhanced by systemic factors such as alterations in respiratory control, or differential hormonal patterns.
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En línea:
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http://repositorio.upch.edu.pe/handle/upch/7360
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