title: Crucial Role of FLVCR1a in the Maintenance of Intestinal Heme Homeostasis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  By exporting the excess of de novo synthesized heme from intestinal cells, FLVCR1a participates in the control of intestinal mucosa homeostasis.
authors.affiliation: 1 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy .
authors.forename: Veronica
authors.initials: V
authors.lastname: Fiorito
authors.affiliation: 2 EuroClone S.p.A Research Laboratory, Molecular Biotechnology Centre (MBC), University of Torino , Torino, Italy .
authors.forename: Marco
authors.initials: M
authors.lastname: Forni
authors.affiliation: 1 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy .
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
authors.affiliation: 1 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy .
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.affiliation: 1 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy .
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D049109:Cell Proliferation; D055786:Gene Knockout Techniques; D006418:Heme / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism
chemical_list: C492690:FLVCR1 protein, human; C526650:Flvcr1 protein, mouse; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; D011991:Receptors, Virus; D006418:Heme