Veronica Fiorito1, Marco Forni2, Lorenzo Silengo1, Fiorella Altruda1, Emanuela Tolosano1. 1. 1 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy . 2. 2 EuroClone S.p.A Research Laboratory, Molecular Biotechnology Centre (MBC), University of Torino , Torino, Italy .
Abstract
AIMS: The maintenance of heme homeostasis, mucosa cell renewal, and redox environment in the intestine is essential to permit digestion, absorption, cell proliferation, cell apoptosis, and immune response and to avoid the development of gut disorders. The feline leukemia virus, subgroup C, receptor 1a (FLVCR1a) is a heme exporter expressed in almost all cell types, including intestinal cells. This work investigates the role of FLVCR1a in the intestine, taking advantage of an intestine-specific conditional Flvcr1a-knockout mouse and of FLVCR1a-depleted Caco2 cells. RESULTS: The data show that FLVCR1a does not participate in the absorption of dietary heme, whereas it is involved in the export of de novo synthesized heme from intestinal cells. The loss of Flvcr1a is associated with a decrease of intestinal cell proliferation and with alterations in the peculiar homeostasis of proliferating cells, including the maintenance of their redox status. The involvement of FLVCR1a in these processes renders this exporter crucial for the survival of mice in a model of ulcerative colitis. INNOVATION: These findings shed light on the role of heme export in the dietary heme absorption process and unravel a new role for heme export in the control of mucosal renewal and in proliferating cell redox status and metabolic activity, demonstrating a crucial role for FLVCR1a in maintaining intestinal homeostasis in both physiologic and pathologic situations. CONCLUSION: By exporting the excess of de novo synthesized heme from intestinal cells, FLVCR1a participates in the control of intestinal mucosa homeostasis.
AIMS: The maintenance of heme homeostasis, mucosa cell renewal, and redox environment in the intestine is essential to permit digestion, absorption, cell proliferation, cell apoptosis, and immune response and to avoid the development of gut disorders. The feline leukemia virus, subgroup C, receptor 1a (FLVCR1a) is a heme exporter expressed in almost all cell types, including intestinal cells. This work investigates the role of FLVCR1a in the intestine, taking advantage of an intestine-specific conditional Flvcr1a-knockout mouse and of FLVCR1a-depleted Caco2 cells. RESULTS: The data show that FLVCR1a does not participate in the absorption of dietary heme, whereas it is involved in the export of de novo synthesized heme from intestinal cells. The loss of Flvcr1a is associated with a decrease of intestinal cell proliferation and with alterations in the peculiar homeostasis of proliferating cells, including the maintenance of their redox status. The involvement of FLVCR1a in these processes renders this exporter crucial for the survival of mice in a model of ulcerative colitis. INNOVATION: These findings shed light on the role of heme export in the dietary heme absorption process and unravel a new role for heme export in the control of mucosal renewal and in proliferating cell redox status and metabolic activity, demonstrating a crucial role for FLVCR1a in maintaining intestinal homeostasis in both physiologic and pathologic situations. CONCLUSION: By exporting the excess of de novo synthesized heme from intestinal cells, FLVCR1a participates in the control of intestinal mucosa homeostasis.
Authors: Robert Staroń; Paweł Lipiński; Małgorzata Lenartowicz; Aleksandra Bednarz; Anna Gajowiak; Ewa Smuda; Wojciech Krzeptowski; Marek Pieszka; Tamara Korolonek; Iqbal Hamza; Dorine W Swinkels; Rachel P L Van Swelm; Rafał R Starzyński Journal: PLoS One Date: 2017-07-13 Impact factor: 3.240
Authors: Deborah Chiabrando; Marco Castori; Maja di Rocco; Martin Ungelenk; Sebastian Gießelmann; Matteo Di Capua; Annalisa Madeo; Paola Grammatico; Sophie Bartsch; Christian A Hübner; Fiorella Altruda; Lorenzo Silengo; Emanuela Tolosano; Ingo Kurth Journal: PLoS Genet Date: 2016-12-06 Impact factor: 5.917
Authors: José María Moreno-Navarrete; Amaia Rodríguez; Francisco Ortega; Sara Becerril; Mònica Sabater-Masdeu; Jessica Latorre; Wifredo Ricart; Gema Frühbeck; José Manuel Fernández-Real Journal: Sci Rep Date: 2017-07-13 Impact factor: 4.379