• MeSH
• analgezie * MeSH
• bolest farmakoterapie   MeSH
• COVID-19 * MeSH
• lidé MeSH
• neuropilin-1 metabolismus   MeSH
• receptory vaskulárního endoteliálního růstového faktoru metabolismus   MeSH
• SARS-CoV-2 metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH
• Názvy látek
• neuropilin-1 MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• vaskulární endoteliální růstový faktor A MeSH

With hypoxic stress, hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are elevated and their responses are altered in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (Ochotona curzoniae)] as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. The results indicate that HIF-1alpha and VEGF are engaged in physiological functions under hypoxic environment. The purpose of the current study was to examine the protein levels of VEGF receptor subtypes (VEGFRs: VEGFR-1, VEGFR-2 and VEGFR-3) in the end organs, namely skeletal muscle, heart and lung in response to hypoxic stress. ELISA and Western blot analysis were employed to determine HIF-1alpha and the protein expression of VEGFRs in control animals and plateau pikas. We further blocked HIF-1alpha signal to determine if HIF-1alpha regulates alternations in VEGFRs in those tissues. We hypothesized that responsiveness of VEGFRs in the major end organs of plateau animals is differential with insult of hypoxic stress and is modulated by low oxygen sensitive HIF-1alpha. Our results show that hypoxic stress induced by exposure of lower O(2) for 6 h significantly increased the levels of VEGFR-2 in skeletal muscle, heart and lung and the increases were amplified in plateau pikas. Our results also demonstrate that hypoxic stress enhanced VEGFR-3 in lungs of plateau animals. Nonetheless, no significant alternations in VEGFR-1 were observed in those tissues with hypoxic stress. Moreover, we observed decreases of VEGFR-2 in skeletal muscle, heart and lung; and decreases of VEGFR-3 in lung following HIF-1alpha inhibition. Overall, our findings suggest that in plateau animals 1) responsiveness of VEGFRs is different under hypoxic environment; 2) amplified VEGFR-2 response appears in skeletal muscle, heart and lung, and enhanced VEGFR-3 response is mainly observed in lung; 3) HIF-1alpha plays a regulatory role in the levels of VEGFRs. Our results provide the underlying cellular and molecular mechanisms responsible for hypoxic environment in plateau animals, having an impact on research of physiological and ecological adaptive responses to acute or chronic hypoxic stress in humans who living at high attitude and who live at a normal sea level but suffer from hypoxic disorders.

• MeSH
• aklimatizace MeSH
• druhová specificita MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   MeSH
• fyziologický stres MeSH
• hypoxie metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• Lagomorpha metabolismus   MeSH
• myokard metabolismus   MeSH
• nadmořská výška MeSH
• orgánová specificita fyziologie   MeSH
• plíce metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• receptory vaskulárního endoteliálního růstového faktoru metabolismus   MeSH
• regulace genové exprese fyziologie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Tibet MeSH
• Názvy látek
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH

Vascular endothelial growth factors (VEGFs) have a leading role among variety of angiogenic factors. Together with their receptors, they play an important role in endothelial cell proliferation and/or elongation, migration and vascular morphogenesis. In order to determine their possible role in malignant melanoma progression, VEGF (representing VEGFA), VEGF-C and VEGFR-1, -2, -3 immunohistochemical expression on formalin-fixed, paraffin-embedded tissue sections were evaluated. A total of 196 tissue samples consisting of 130 malignant melanomas (MM) with various vertical depth of invasion, 15 metastatic melanomas, and 66 nevi including dysplastic nevi and melanocytic nevi were analysed. Production of both VEGFs were common in benign melanocytic tumors while MM exhibited significant upregulation of VEGF (p<0.0027) and VEGF-C (p<0.0001). The proteins were also detected within stromal cells surrounding tumors, particularly in fibrocytes/ fibroblasts, macrophages and endothelial cells. They also exhibited significant increase in malignant lesions (p<0.0001). VEGFRs were localized in tumor, as well in stromal cells. Although expression of VEGF receptors was significantly higher in MM versus nevi (p<0.002 for VEGFR-1, p<0.004 for VEGFR-2 and p<0.0001 for VEGFR-3), a considerable percentage of MM were negative. There were no correlations between sentinel node positivity and all investigated proteins. When clinical outcome was evaluated, progression of the disease positively correlated with VEGF (p<0,007) and VEGF-C (p<0,008) expression VEGF (p<0.001) and VEGF-C (p<0.0001) positively correlated with nestin expression in the capillary endothelium, which was used for angiogenesis detection. Our work demonstrated that upregulation of VEGFs is associated with progression of malignant melanomas. The protein expression in the tumor microenvironment highlights their importance in malignant stromal phenotype which may serve as a potential target for the anticancer therapy.

• MeSH
• cévní endotel metabolismus   MeSH
• lidé MeSH
• melanom metabolismus   patologie   MeSH
• nádory kůže metabolismus   patologie   MeSH
• nestin MeSH
• prognóza MeSH
• proteiny intermediálních filament metabolismus   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptor 3 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptory vaskulárního endoteliálního růstového faktoru metabolismus   MeSH
• vaskulární endoteliální růstové faktory metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• vaskulární endoteliální růstový faktor C metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• NES protein, human MeSH Prohlížeč
• nestin MeSH
• proteiny intermediálních filament MeSH
• proteiny nervové tkáně MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor MeSH
• receptor 3 pro vaskulární endoteliální růstový faktor MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• vaskulární endoteliální růstové faktory MeSH
• vaskulární endoteliální růstový faktor A MeSH
• vaskulární endoteliální růstový faktor C MeSH