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The role of HIF-1α in the regulation of cardiomyogenesis in vitro

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KUDOVÁ Jana PROCHÁZKOVÁ Jiřina VAŠÍČEK Ondřej BINÓ Lucia KOLÁŘOVÁ Hana SÝKOROVÁ Dominika KARAS Pavel PACHERNÍK Jiří KUBALA Lukáš

Rok publikování 2014
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Citace
Popis A cardiac cell formation (cardiomyogenesis) is critically dependent on cell microenvironment. Oxygen availability is one of the most important factors which plays an essential role in cardiomyocytes differentiation. It is known that hypoxia (a low oxygen level) modulates the differentiation of murine embryonic stem cells to cardiomyocytes in vitro. Hypoxic conditions lead to the stabilization of hypoxia-inducible factor-1 alpha (HIF-1alpha), the central mediator of cellular transcription responses to oxygen tension. However, the role of HIF-1alpha in the regulation of cardiomyocyte differentiation is not well understood. With the aim of better understanding the role of HIF-1alpha within cardiomyocyte development and progenitor cell reprogramming, cardiomyogenesis in wild type and HIF-1alpha depleted murine embryonic stem cells was analyzed in vitro. The level of expression of individual cardiospecific genes was higher in the HIF-1alpha deficient cell line compared to wild type cells in the early phase of differentiation (on Day 5). In contrast, in the late phase of cardiac cell development (on Day 15 and later), these markers were lower in HIF-1alpha deficient cells. This suggests a higher state of maturity in HIF-1alpha deficient cells at the beginning of cardiomyogenesis differentiation. At the same time, the profile of cardiospecific markers suggests that a lower number of progenitor cells enter the differentiation process. In conclusion, HIF-1alpha is important for induction of the development of cardiomyogenic progenitors and has a significant effect on the maturation of early cardiomyocytes in in vitro culture.