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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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dc.contributor.author Bermudez, Daniela
dc.contributor.author Azad, Priti
dc.contributor.author Figueroa-Mujica, Romulo
dc.contributor.author Vizcardo-Galindo, Gustavo
dc.contributor.author Corante, Noemi
dc.contributor.author Guerra-Giraldez, Cristina
dc.contributor.author Haddad, Gabriel G.
dc.contributor.author Villafuerte, Francisco C.
dc.date.accessioned 2019-12-06T20:57:40Z
dc.date.available 2019-12-06T20:57:40Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/7360
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher American Physiological Society
dc.relation.ispartof urn:issn:1522-1490
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject Chronic Disease en_US
dc.subject Genetic Predisposition to Disease en_US
dc.subject Altitude en_US
dc.subject Andean en_US
dc.subject chronic mountain sickness en_US
dc.subject erythropoiesis en_US
dc.subject excessive erythrocytosis en_US
dc.subject high altitude en_US
dc.subject Altitude Sickness/epidemiology en_US
dc.subject Erythroid Precursor Cells/metabolism en_US
dc.subject Erythropoietin/blood en_US
dc.subject Gene Expression Regulation/drug effects en_US
dc.subject Homeostasis en_US
dc.subject Hypoxia en_US
dc.subject Iron/metabolism en_US
dc.subject Leukocytes, Mononuclear en_US
dc.subject Oxygen/metabolism/pharmacology en_US
dc.subject Transcriptome en_US
dc.title Increased hypoxic proliferative response and gene expression in erythroid progenitor cells of Andean highlanders with Chronic Mountain Sickness. en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1152/ajpregu.00250.2019
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE


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