Browsing by Author "Martelli, Fabio"

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    Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation
    (American Association for the Advancement of Science, 2021-05-07) Virga, Federico; Cappellesso, Federica; Stijlemans, Benoit; Henze, Anne-Theres; Trotta, Rosa; Van Audenaerde, Jonas; Mirchandani, Ananda S.; Sanchez-Garcia, Manuel A.; Vandewalle, Jolien; Orso, Francesca; Riera-Domingo, Carla; Griffa, Alberto; Ivan, Cristina; Smits, Evelien; Laoui, Damya; Martelli, Fabio; Langouche, Lies; Van den Berghe, Greet; Feron, Olivier; Ghesquière, Bart; Prenen, Hans; Libert, Claude; Walmsley, Sarah R.; Corbet, Cyril; Van Ginderachter, Jo A.; Ivan, Mircea; Taverna, Daniela; Mazzone, Massimiliano; Medicine, School of Medicine
    Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210-based therapeutic and diagnostic strategies.
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    miR-210: More than a silent player in hypoxi
    (Wiley, 2011-02) Devlin, Cecilia; Greco, Simona; Martelli, Fabio; Ivan, Mircea; Department of Medicine, IU School of Medicine
    Multiple studies have consistently established that miR (microRNA)-210 induction is a feature of the hypoxic response in both normal and transformed cells. Here, we discuss the emerging biochemical functions of this miRNA and anticipate potential clinical applications. miR-210 is a robust target of hypoxia-inducible factor, and its overexpression has been detected in a variety of cardiovascular diseases and solid tumors. High levels of miR-210 have been linked to an in vivo hypoxic signature and associated with adverse prognosis in cancer patients. A wide spectrum of miR-210 targets have been identified, with roles in mitochondrial metabolism, angiogenesis, DNA repair, and cell survival. Such targets may broadly affect the evolution of tumors and other pathological settings, such as ischemic disorders. Harnessing the knowledge of miR-210's actions may lead to novel diagnostic and therapeutic approaches.