{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA large body of work has detailed the regulatory network that maintains systemic iron homeostasis. Numerous studies have focused on the HFE protein and its interactions with transferrin receptors—principally TfR1 and TfR2—to modulate the expression of hepcidin, the key hepatic hormone controlling iron absorption and release. These investigations demonstrate that perturbations in HFE function, such as those seen in hereditary hemochromatosis, result in altered hepcidin production and subsequent iron overload, thereby underpinning the disease’s pathogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther reports have expanded our understanding by elucidating additional signaling pathways and tissue‐specific responses that influence iron metabolism. These studies highlight how factors such as BMP/SMAD and MAPK signaling, along with TLR4‐mediated inflammatory responses, contribute to the fine tuning of hepcidin expression and iron distribution in organs as diverse as the liver, retina, and even the brain. They underscore the roles of protein–protein interactions (including effects on ALK3 stabilization and transferrin uptake) and oxidative stress in shaping the clinical course of iron overload and related disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNotably, despite the wealth of information regarding the molecular pathways governing iron uptake, storage, and inflammatory modulation, none of the provided abstracts describe or allude to a role for PPP2R3B. In the context of these studies—which emphasize HFE, its interacting partners, and the regulation of hepcidin via multiple signaling cascades—the function of PPP2R3B remains uncharacterized. Thus, while these papers offer comprehensive insight into iron homeostasis and the pathogenesis of iron overload disorders, they do not address whether PPP2R3B contributes to these processes. This absence indicates a gap in the literature and suggests that the potential involvement of PPP2R3B in iron regulation, signal transduction, or cellular metabolism warrants further investigation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "38"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Debbie Trinder, John K Olynyk, William S Sly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.082112299"}], "href": "https://doi.org/10.1073/pnas.082112299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11943867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11943867"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Richard S Ajioka, Joanne E Levy, Nancy C Andrews, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of iron absorption in Hfe mutant mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2001-11-0037"}], "href": "https://doi.org/10.1182/blood-2001-11-0037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12149232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12149232"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Gaël Nicolas, Lydie Viatte, Dan-Qing Lou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1150"}], "href": "https://doi.org/10.1038/ng1150"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12704388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12704388"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Thomas Herrmann, Martina Muckenthaler, Frank van der Hoeven, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Med (Berl) (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00109-003-0508-x"}], "href": "https://doi.org/10.1007/s00109-003-0508-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14618243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14618243"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gaël Nicolas, Nancy C Andrews, Axel Kahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepcidin, a candidate modifier of the hemochromatosis phenotype in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-09-3358"}], "href": "https://doi.org/10.1182/blood-2003-09-3358"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14656876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14656876"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Pauline Lee, Hongfan Peng, Terri Gelbart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0403108101"}], "href": "https://doi.org/10.1073/pnas.0403108101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15192150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15192150"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hortence Makui, Ricardo J Soares, Wenlei Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-02-0629"}], "href": "https://doi.org/10.1182/blood-2005-02-0629"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15914561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15914561"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Marco Constante, Wenlei Jiang, Dongmei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00092.2006"}], "href": "https://doi.org/10.1152/ajpgi.00092.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16565419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16565419"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Tapasree Goswami, Nancy C Andrews "}, {"type": "b", "children": [{"type": "t", "text": "Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C600197200"}], "href": "https://doi.org/10.1074/jbc.C600197200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16893896"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16893896"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Marco Constante, Dongmei Wang, Valérie-Ann Raymond, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Repression of repulsive guidance molecule C during inflammation is independent of Hfe and involves tumor necrosis factor-alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2007.060437"}], "href": "https://doi.org/10.2353/ajpath.2007.060437"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17255318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17255318"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Maja Vujic Spasic, Judit Kiss, Thomas Herrmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physiologic systemic iron metabolism in mice deficient for duodenal Hfe."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-07-036186"}], "href": "https://doi.org/10.1182/blood-2006-07-036186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17264297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17264297"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jingyu Huang, J Scott Gabrielsen, Robert C Cooksey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased glucose disposal and AMP-dependent kinase signaling in a mouse model of hemochromatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703625200"}], "href": "https://doi.org/10.1074/jbc.M703625200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17971451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17971451"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jaya P Gnana-Prakasam, Pamela M Martin, Barbara A Mysona, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/Toll-like receptor-4 pathway independent of Hfe."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20071377"}], "href": "https://doi.org/10.1042/BJ20071377"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18042040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18042040"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Maja Vujić Spasić, Judit Kiss, Thomas Herrmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hfe acts in hepatocytes to prevent hemochromatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2007.11.014"}], "href": "https://doi.org/10.1016/j.cmet.2007.11.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18249176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18249176"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Paul J Schmidt, Paul T Toran, Anthony M Giannetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2007.11.016"}], "href": "https://doi.org/10.1016/j.cmet.2007.11.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18316026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18316026"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Anita C G Chua, Carly E Herbison, Sarah F Drake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of Hfe in transferrin-bound iron uptake by hepatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.22180"}], "href": "https://doi.org/10.1002/hep.22180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18393371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18393371"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Mandy L Heritage, Therese L Murphy, Kim R Bridle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alcohol Clin Exp Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1530-0277.2009.00969.x"}], "href": "https://doi.org/10.1111/j.1530-0277.2009.00969.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19426170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19426170"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Manfred Nairz, Igor Theurl, Andrea Schroll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absence of functional Hfe protects mice from invasive Salmonella enterica serovar Typhimurium infection via induction of lipocalin-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-05-223354"}], "href": "https://doi.org/10.1182/blood-2009-05-223354"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19700664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19700664"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jaya P Gnana-Prakasam, Muthusamy Thangaraju, Kebin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absence of iron-regulatory protein Hfe results in hyperproliferation of retinal pigment epithelium: role of cystine/glutamate exchanger."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20090424"}], "href": "https://doi.org/10.1042/BJ20090424"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19715555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19715555"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Lijian Wang, Lynne Harrington, Estela Trebicka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI39939"}], "href": "https://doi.org/10.1172/JCI39939"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19809161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19809161"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Daniel F Wallace, Lesa Summerville, Emily M Crampton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.23198"}], "href": "https://doi.org/10.1002/hep.23198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19824072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19824072"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Junwei Gao, Juxing Chen, Ivana De Domenico, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-09-245209"}], "href": "https://doi.org/10.1182/blood-2009-09-245209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20177050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20177050"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Cinzia Garuti, Yinghua Tian, Giuliana Montosi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepcidin expression does not rescue the iron-poor phenotype of Kupffer cells in Hfe-null mice after liver transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2010.03.043"}], "href": "https://doi.org/10.1053/j.gastro.2010.03.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20338170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20338170"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Pedro Ramos, Ella Guy, Nan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced erythropoiesis in Hfe-KO mice indicates a role for Hfe in the modulation of erythroid iron homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-09-307462"}], "href": "https://doi.org/10.1182/blood-2010-09-307462"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21059897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21059897"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Yiting Liu, Sang Y Lee, Elizabeth Neely, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant HFE H63D protein is associated with prolonged endoplasmic reticulum stress and increased neuronal vulnerability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.170944"}], "href": "https://doi.org/10.1074/jbc.M110.170944"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21349849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21349849"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Karin E Finberg, Rebecca L Whittlesey, Nancy C Andrews "}, {"type": "b", "children": [{"type": "t", "text": "Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-10-315507"}], "href": "https://doi.org/10.1182/blood-2010-10-315507"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21355094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21355094"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Pauline Lee, Mei-Hui Hsu, Jennifer Welser-Alves, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Severe microcytic anemia but increased erythropoiesis in mice lacking Hfe or Tfr2 and Tmprss6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cells Mol Dis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcmd.2011.12.005"}], "href": "https://doi.org/10.1016/j.bcmd.2011.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22244935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22244935"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Roheeth D Delima, Anita C G Chua, Janina E E Tirnitz-Parker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of hemochromatosis protein and transferrin receptor 2 causes iron-induced liver injury in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.25689"}], "href": "https://doi.org/10.1002/hep.25689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22383097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22383097"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Wint Nandar, Elizabeth B Neely, Erica Unger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2013.02.009"}], "href": "https://doi.org/10.1016/j.bbadis.2013.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23429074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23429074"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Gautam Rishi, Emily M Crampton, Daniel F Wallace, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In situ proximity ligation assays indicate that hemochromatosis proteins Hfe and transferrin receptor 2 (Tfr2) do not interact."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0077267"}], "href": "https://doi.org/10.1371/journal.pone.0077267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24155934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24155934"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Fatima Ali-Rahmani, Patricia S Grigson, Sang Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "H63D mutation in hemochromatosis alters cholesterol metabolism and induces memory impairment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2013.12.014"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2013.12.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24439478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24439478"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Patricia Kent, Nicole Wilkinson, Marco Constante, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hfe and Hjv exhibit overlapping functions for iron signaling to hepcidin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Med (Berl) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00109-015-1253-7"}], "href": "https://doi.org/10.1007/s00109-015-1253-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25609138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25609138"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Kari A Duck, Elizabeth B Neely, Ian A Simpson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for sex and a common HFE gene variant in brain iron uptake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cereb Blood Flow Metab (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0271678X17701949"}], "href": "https://doi.org/10.1177/0271678X17701949"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28350201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28350201"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Márcio Simão, António Camacho, Agnès Ostertag, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0207441"}], "href": "https://doi.org/10.1371/journal.pone.0207441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30427936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30427936"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Márcio Simão, Paulo J Gavaia, António Camacho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intracellular iron uptake is favored in Hfe-KO mouse primary chondrocytes mimicking an osteoarthritis-related phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biofactors (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/biof.1520"}], "href": "https://doi.org/10.1002/biof.1520"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31132316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31132316"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Kapil Chaudhary, Aruna Chilakala, Sudha Ananth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Renal iron accelerates the progression of diabetic nephropathy in the HFE gene knockout mouse model of iron overload."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00184.2019"}], "href": "https://doi.org/10.1152/ajprenal.00184.2019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31188032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31188032"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Egon Demetz, Piotr Tymoszuk, Richard Hilbe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The haemochromatosis gene Hfe and Kupffer cells control LDL cholesterol homeostasis and impact on atherosclerosis development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Heart J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/eurheartj/ehaa140"}], "href": "https://doi.org/10.1093/eurheartj/ehaa140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32227235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32227235"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Juan Liu, Xiaopeng Wu, Hailong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HFE inhibits type I IFNs signaling by targeting the SQSTM1-mediated MAVS autophagic degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2020.1804683"}], "href": "https://doi.org/10.1080/15548627.2020.1804683"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32746697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32746697"}]}]}]}