Beschreibung:
<jats:p>A microenvironment low in O<sub>2</sub> (‘physiological' hypoxia) governs the functions of perivascular multipotent mesenchymal stromal cells, defining their involvement in tissue physiological homeostasis and regenerative remodelling. Acute hypoxic stress is considered as one of the important factors inducing tissue damage. Here, we evaluate the influence of short-term hypoxia (1% O<sub>2</sub> for 24 h) on perivascular adipose tissue-derived cells (ASCs) permanently expanded in tissue-related O<sub>2</sub> (5%) microenvironment. After hypoxic exposure, ASCs retained high viability, stromal cell morphology and mesenchymal phenotype (CD73+, CD90+, CD105+ and CD45-). Mild oxidative damage was unveiled as elevation of reactive oxygen species and thiobarbituric acid-active products, while no reduction in the activity of the antioxidant enzymes catalase and glutathione peroxidase and a 20% statistically significant increase in superoxide dismutase activity was detected. Expression of hypoxia-inducible factor <i>(HIF)-1α</i> and <i>HIF-3α</i> isoforms was differently regulated. <i>HIF-1α</i> displayed transient up-regulation, with maximum levels 30 min after acute hypoxic exposure, while <i>HIF-3α</i> was significantly up-regulated after 24 h. Up-regulation of <i>ERK7, MEK1 </i>and <i>c-fos</i>, and down-regulation of <i>MKK6, p53</i>, <i>CCNA2</i>, <i>CCNB1</i> and<i> CCNB2</i> were observed after 24 h of oxygen deprivation. Acute hypoxic exposure did not affect the gene expression of other mitogen-activated protein kinases <i>(MAPKs)</i> and <i>MAPK</i> kinases, <i>MAPK/ERK</i> kinase-interacting proteins, <i>MAPK</i>-activated transcription factors and scaffolding proteins. Significant stimulation of vascular endothelial growth factor α and interleukin-6 production was detected in ASC-conditioned medium. Thus, tissue O<sub>2</sub>-adapted ASCs are resistant to hypoxic stress, which can ensure their effective involvement in the regeneration of tissue damage under significant oxygen deprivation.</jats:p>