Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell‐line HepG2 induced by thalassaemic sera
Summary β‐Thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of β‐thalassaemia, we observed that the liver expressed relatively low levels of hepcidin, which is a key factor in the regulation of iron absorption by the gu...
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| creator | Weizer‐Stern, Orly Adamsky, Konstantin Amariglio, Ninette Levin, Carina Koren, Ariel Breuer, William Rachmilewitz, Eliezer Breda, Laura Rivella, Stefano Ioav Cabantchik, Z. Rechavi, Gideon |
| description | Summary
β‐Thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of β‐thalassaemia, we observed that the liver expressed relatively low levels of hepcidin, which is a key factor in the regulation of iron absorption by the gut and of iron recycling by the reticuloendothelial system. It was hypothesised that, despite the overt iron overload, a putative plasma factor found in β‐thalassaemia might suppress liver hepcidin expression. Sera from β‐thalassaemia and haemochromatosis (C282Y mutation) patients were compared with those of healthy individuals regarding their capacity to induce changes the expression of key genes of iron metabolism in human HepG2 hepatoma cells. Sera from β‐thalassaemia major patients induced a major decrease in hepcidin (HAMP) and lipocalin2 (oncogene 24p3) (LCN2) expression, as well as a moderate decrease in haemojuvelin (HFE2) expression, compared with sera from healthy individuals. A significant correlation was found between the degree of downregulation of HAMP and HFE2 induced by β‐thalassaemia major sera (r = 0·852, P |
| doi_str_mv | 10.1111/j.1365-2141.2006.06258.x |
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β‐Thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of β‐thalassaemia, we observed that the liver expressed relatively low levels of hepcidin, which is a key factor in the regulation of iron absorption by the gut and of iron recycling by the reticuloendothelial system. It was hypothesised that, despite the overt iron overload, a putative plasma factor found in β‐thalassaemia might suppress liver hepcidin expression. Sera from β‐thalassaemia and haemochromatosis (C282Y mutation) patients were compared with those of healthy individuals regarding their capacity to induce changes the expression of key genes of iron metabolism in human HepG2 hepatoma cells. Sera from β‐thalassaemia major patients induced a major decrease in hepcidin (HAMP) and lipocalin2 (oncogene 24p3) (LCN2) expression, as well as a moderate decrease in haemojuvelin (HFE2) expression, compared with sera from healthy individuals. A significant correlation was found between the degree of downregulation of HAMP and HFE2 induced by β‐thalassaemia major sera (r = 0·852, P < 0·0009). Decreased HAMP expression was also found in HepG2 cells treated with sera from β‐thalassaemia intermedia patients. In contrast, the majority of sera from hereditary haemochromatosis patients induced an increase in HAMP expression, which correlated with transferrin (Tf) saturation (r = 0·765, P < 0·0099). Our results suggest that, in β‐thalassaemia, serum factors might override the potential effect of iron overload on HAMP expression, thereby providing an explanation for the failure to arrest excessive intestinal iron absorption in these patients.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/j.1365-2141.2006.06258.x</identifier><identifier>PMID: 16939499</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Acute-Phase Proteins - biosynthesis ; Acute-Phase Proteins - genetics ; Anemias. Hemoglobinopathies ; Antimicrobial Cationic Peptides - biosynthesis ; Antimicrobial Cationic Peptides - genetics ; beta-Thalassemia - blood ; beta-Thalassemia - therapy ; Biological and medical sciences ; Blood Transfusion ; Cell Line ; Diseases of red blood cells ; Down-Regulation ; GPI-Linked Proteins ; haemochromatosis ; haemojuvelin ; Hematologic and hematopoietic diseases ; Hemochromatosis - blood ; Hepatocytes - metabolism ; hepcidin ; Hepcidins ; Humans ; iron ; Lipocalin-2 ; Lipocalins ; Medical sciences ; Membrane Proteins - biosynthesis ; Membrane Proteins - genetics ; Metabolic diseases ; Metals (hemochromatosis...) ; Other metabolic disorders ; Polymerase Chain Reaction - methods ; Proto-Oncogene Proteins - biosynthesis ; Proto-Oncogene Proteins - genetics ; thalassaemia</subject><ispartof>British journal of haematology, 2006-10, Vol.135 (1), p.129-138</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5138-fca29796165d9c738208faf723ad16e757b8ad45490180dd5939ea5ca85161703</citedby><cites>FETCH-LOGICAL-c5138-fca29796165d9c738208faf723ad16e757b8ad45490180dd5939ea5ca85161703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2141.2006.06258.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2141.2006.06258.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18090144$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16939499$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weizer‐Stern, Orly</creatorcontrib><creatorcontrib>Adamsky, Konstantin</creatorcontrib><creatorcontrib>Amariglio, Ninette</creatorcontrib><creatorcontrib>Levin, Carina</creatorcontrib><creatorcontrib>Koren, Ariel</creatorcontrib><creatorcontrib>Breuer, William</creatorcontrib><creatorcontrib>Rachmilewitz, Eliezer</creatorcontrib><creatorcontrib>Breda, Laura</creatorcontrib><creatorcontrib>Rivella, Stefano</creatorcontrib><creatorcontrib>Ioav Cabantchik, Z.</creatorcontrib><creatorcontrib>Rechavi, Gideon</creatorcontrib><title>Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell‐line HepG2 induced by thalassaemic sera</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
β‐Thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of β‐thalassaemia, we observed that the liver expressed relatively low levels of hepcidin, which is a key factor in the regulation of iron absorption by the gut and of iron recycling by the reticuloendothelial system. It was hypothesised that, despite the overt iron overload, a putative plasma factor found in β‐thalassaemia might suppress liver hepcidin expression. Sera from β‐thalassaemia and haemochromatosis (C282Y mutation) patients were compared with those of healthy individuals regarding their capacity to induce changes the expression of key genes of iron metabolism in human HepG2 hepatoma cells. Sera from β‐thalassaemia major patients induced a major decrease in hepcidin (HAMP) and lipocalin2 (oncogene 24p3) (LCN2) expression, as well as a moderate decrease in haemojuvelin (HFE2) expression, compared with sera from healthy individuals. A significant correlation was found between the degree of downregulation of HAMP and HFE2 induced by β‐thalassaemia major sera (r = 0·852, P < 0·0009). Decreased HAMP expression was also found in HepG2 cells treated with sera from β‐thalassaemia intermedia patients. In contrast, the majority of sera from hereditary haemochromatosis patients induced an increase in HAMP expression, which correlated with transferrin (Tf) saturation (r = 0·765, P < 0·0099). Our results suggest that, in β‐thalassaemia, serum factors might override the potential effect of iron overload on HAMP expression, thereby providing an explanation for the failure to arrest excessive intestinal iron absorption in these patients.</description><subject>Acute-Phase Proteins - biosynthesis</subject><subject>Acute-Phase Proteins - genetics</subject><subject>Anemias. Hemoglobinopathies</subject><subject>Antimicrobial Cationic Peptides - biosynthesis</subject><subject>Antimicrobial Cationic Peptides - genetics</subject><subject>beta-Thalassemia - blood</subject><subject>beta-Thalassemia - therapy</subject><subject>Biological and medical sciences</subject><subject>Blood Transfusion</subject><subject>Cell Line</subject><subject>Diseases of red blood cells</subject><subject>Down-Regulation</subject><subject>GPI-Linked Proteins</subject><subject>haemochromatosis</subject><subject>haemojuvelin</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hemochromatosis - blood</subject><subject>Hepatocytes - metabolism</subject><subject>hepcidin</subject><subject>Hepcidins</subject><subject>Humans</subject><subject>iron</subject><subject>Lipocalin-2</subject><subject>Lipocalins</subject><subject>Medical sciences</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Membrane Proteins - genetics</subject><subject>Metabolic diseases</subject><subject>Metals (hemochromatosis...)</subject><subject>Other metabolic disorders</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Proto-Oncogene Proteins - biosynthesis</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>thalassaemia</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMty0zAUhjUMDE1bXoHRpuzsStbF8oIFFNrAdIYNXWtOpGPijGO7kk2SXR-BZ-RJkEmGbtFGt-8c_foIoZzlPI3rTc6FVlnBJc8LxnTOdKFMvn9BFv8uXpIFY6zMOJPmjJzHuGGMC6b4a3LGdSUqWVULsvvU77qAP6YWxqbvaF_TNQ6u8U1HofN0DbjtN9NPbNMB7oeAMc5c2o1rnFkYe3cYkTps299PvxKHdInDXZEYPzn0dHVILLQQY2rWOBoxwCV5VUMb8c1pviAPt5-_3yyz-293X24-3GdOcWGy2kFRlZXmWvnKlcIUzNRQl4UAzzWWqlwZ8FLJinHDvFfpXwjKgVFc85KJC_Lu2HcI_eOEcbTbJs5RocN-ilYbI4UseALNEXShjzFgbYfQbCEcLGd2lm43dnZrZ7d2lm7_Srf7VPr29Ma02qJ_LjxZTsDVCYDooK0DdK6Jz5xhKb6UiXt_5HZNi4f_DmA_fl3OK_EH9hmfAA</recordid><startdate>200610</startdate><enddate>200610</enddate><creator>Weizer‐Stern, Orly</creator><creator>Adamsky, Konstantin</creator><creator>Amariglio, Ninette</creator><creator>Levin, Carina</creator><creator>Koren, Ariel</creator><creator>Breuer, William</creator><creator>Rachmilewitz, Eliezer</creator><creator>Breda, Laura</creator><creator>Rivella, Stefano</creator><creator>Ioav Cabantchik, Z.</creator><creator>Rechavi, Gideon</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200610</creationdate><title>Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell‐line HepG2 induced by thalassaemic sera</title><author>Weizer‐Stern, Orly ; Adamsky, Konstantin ; Amariglio, Ninette ; Levin, Carina ; Koren, Ariel ; Breuer, William ; Rachmilewitz, Eliezer ; Breda, Laura ; Rivella, Stefano ; Ioav Cabantchik, Z. ; Rechavi, Gideon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5138-fca29796165d9c738208faf723ad16e757b8ad45490180dd5939ea5ca85161703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Acute-Phase Proteins - biosynthesis</topic><topic>Acute-Phase Proteins - genetics</topic><topic>Anemias. Hemoglobinopathies</topic><topic>Antimicrobial Cationic Peptides - biosynthesis</topic><topic>Antimicrobial Cationic Peptides - genetics</topic><topic>beta-Thalassemia - blood</topic><topic>beta-Thalassemia - therapy</topic><topic>Biological and medical sciences</topic><topic>Blood Transfusion</topic><topic>Cell Line</topic><topic>Diseases of red blood cells</topic><topic>Down-Regulation</topic><topic>GPI-Linked Proteins</topic><topic>haemochromatosis</topic><topic>haemojuvelin</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hemochromatosis - blood</topic><topic>Hepatocytes - metabolism</topic><topic>hepcidin</topic><topic>Hepcidins</topic><topic>Humans</topic><topic>iron</topic><topic>Lipocalin-2</topic><topic>Lipocalins</topic><topic>Medical sciences</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Membrane Proteins - genetics</topic><topic>Metabolic diseases</topic><topic>Metals (hemochromatosis...)</topic><topic>Other metabolic disorders</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Proto-Oncogene Proteins - biosynthesis</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>thalassaemia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Weizer‐Stern, Orly</creatorcontrib><creatorcontrib>Adamsky, Konstantin</creatorcontrib><creatorcontrib>Amariglio, Ninette</creatorcontrib><creatorcontrib>Levin, Carina</creatorcontrib><creatorcontrib>Koren, Ariel</creatorcontrib><creatorcontrib>Breuer, William</creatorcontrib><creatorcontrib>Rachmilewitz, Eliezer</creatorcontrib><creatorcontrib>Breda, Laura</creatorcontrib><creatorcontrib>Rivella, Stefano</creatorcontrib><creatorcontrib>Ioav Cabantchik, Z.</creatorcontrib><creatorcontrib>Rechavi, Gideon</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weizer‐Stern, Orly</au><au>Adamsky, Konstantin</au><au>Amariglio, Ninette</au><au>Levin, Carina</au><au>Koren, Ariel</au><au>Breuer, William</au><au>Rachmilewitz, Eliezer</au><au>Breda, Laura</au><au>Rivella, Stefano</au><au>Ioav Cabantchik, Z.</au><au>Rechavi, Gideon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell‐line HepG2 induced by thalassaemic sera</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2006-10</date><risdate>2006</risdate><volume>135</volume><issue>1</issue><spage>129</spage><epage>138</epage><pages>129-138</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Summary
β‐Thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of β‐thalassaemia, we observed that the liver expressed relatively low levels of hepcidin, which is a key factor in the regulation of iron absorption by the gut and of iron recycling by the reticuloendothelial system. It was hypothesised that, despite the overt iron overload, a putative plasma factor found in β‐thalassaemia might suppress liver hepcidin expression. Sera from β‐thalassaemia and haemochromatosis (C282Y mutation) patients were compared with those of healthy individuals regarding their capacity to induce changes the expression of key genes of iron metabolism in human HepG2 hepatoma cells. Sera from β‐thalassaemia major patients induced a major decrease in hepcidin (HAMP) and lipocalin2 (oncogene 24p3) (LCN2) expression, as well as a moderate decrease in haemojuvelin (HFE2) expression, compared with sera from healthy individuals. A significant correlation was found between the degree of downregulation of HAMP and HFE2 induced by β‐thalassaemia major sera (r = 0·852, P < 0·0009). Decreased HAMP expression was also found in HepG2 cells treated with sera from β‐thalassaemia intermedia patients. In contrast, the majority of sera from hereditary haemochromatosis patients induced an increase in HAMP expression, which correlated with transferrin (Tf) saturation (r = 0·765, P < 0·0099). Our results suggest that, in β‐thalassaemia, serum factors might override the potential effect of iron overload on HAMP expression, thereby providing an explanation for the failure to arrest excessive intestinal iron absorption in these patients.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>16939499</pmid><doi>10.1111/j.1365-2141.2006.06258.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals; Free E-Journal (出版社公開部分のみ）; Wiley Blackwell Single Titles |
| subjects | Acute-Phase Proteins - biosynthesis Acute-Phase Proteins - genetics Anemias. Hemoglobinopathies Antimicrobial Cationic Peptides - biosynthesis Antimicrobial Cationic Peptides - genetics beta-Thalassemia - blood beta-Thalassemia - therapy Biological and medical sciences Blood Transfusion Cell Line Diseases of red blood cells Down-Regulation GPI-Linked Proteins haemochromatosis haemojuvelin Hematologic and hematopoietic diseases Hemochromatosis - blood Hepatocytes - metabolism hepcidin Hepcidins Humans iron Lipocalin-2 Lipocalins Medical sciences Membrane Proteins - biosynthesis Membrane Proteins - genetics Metabolic diseases Metals (hemochromatosis...) Other metabolic disorders Polymerase Chain Reaction - methods Proto-Oncogene Proteins - biosynthesis Proto-Oncogene Proteins - genetics thalassaemia |
| title | Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell‐line HepG2 induced by thalassaemic sera |
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