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Browsing I- Artigos by Author "Arosio, Paolo"
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- Macrophage and epithelial cell H-ferritin expression regulates renal inflammationPublication . Bolisetty, Subhashini; Zarjou, Abolfazl; Hull, Travis D.; Traylor, Amie M.; Perianayagam, Anjana; Joseph, Reny; Kamal, Ahmed I.; Arosio, Paolo; Soares, Miguel P.; Jeney, Viktoria; Balla, Jozsef; George, James F.; Agarwal, AnupamInflammation culminating in fibrosis contributes to progressive kidney disease. Cross-talk between the tubular epithelium and interstitial cells regulates inflammation by a coordinated release of cytokines and chemokines. Here we studied the role of heme oxygenase-1 (HO-1) and the heavy subunit of ferritin (FtH) in macrophage polarization and renal inflammation. Deficiency in HO-1 was associated with increased FtH expression, accumulation of macrophages with a dysregulated polarization profile, and increased fibrosis following unilateral ureteral obstruction in mice: a model of renal inflammation and fibrosis. Macrophage polarization in vitro was predominantly dependent on FtH expression in isolated bone marrow-derived mouse monocytes. Using transgenic mice with conditional deletion of FtH in the proximal tubules (FtH(PT-/-)) or myeloid cells (FtH(LysM-/-)), we found that myeloid FtH deficiency did not affect polarization or accumulation of macrophages in the injured kidney compared with wild-type (FtH(+/+)) controls. However, tubular FtH deletion led to a marked increase in proinflammatory macrophages. Furthermore, injured kidneys from FtH(PT-/-) mice expressed significantly higher levels of inflammatory chemokines and fibrosis compared with kidneys from FtH(+/+) and FtH(LysM-/-) mice. Thus, there are differential effects of FtH in macrophages and epithelial cells, which underscore the critical role of FtH in tubular-macrophage cross-talk during kidney injury.
- The importance of iron in pathophysiologic conditionsPublication . Gozzelino, Raffaella; Arosio, PaoloBiological iron is necessary for vital functions and also potentially toxic to the organisms. This dual effect raised the interest of many investigators to study the mechanisms controlling its homeostasis that are altered in many pathologic conditions. Recently the understanding of iron metabolism significantly improved with the discovery of genes responsible for genetic disorders, such as hemochromatosis, the IRE/IRPs machinery and the hepcidin-ferroportin axis, which allowed to elucidate the basis of cellular and systemic iron homeostasis. In addition, these advances disclosed a causal link between deregulation of iron homeostasis, inflammation and oxidative stress, often induced by the iron accumulation that is commonly observed in many pathologic conditions.