Expression of E-cadherin and other paracellular junction genes is decreased in iron-loaded hepatocytes.
Iron overload in the liver may occur in the clinical conditions hemochromatosis and transfusion-dependent thalassemia or by long-term consumption of large amounts of dietary iron. As iron concentrations increase in the liver, cirrhosis develops, and subsequently the normal architecture of the liver deteriorates. The underlying mechanisms whereby iron loading of hepatocytes leads to the pathology of the liver are not understood. Similarly, a direct relationship between the expression levels of paracellular junction genes and altered hepatocellular physiology has been reported; however, no relationship has been identified between iron loading and the expression of paracellular junction genes. Here, we report that the expression of numerous paracellular junction genes was decreased in iron-loaded hepatocytes, leading to increased cellular permeability, increased baculovirus-mediated gene transfer, and decreased gap junction communication. Iron loading of hepatocytes resulted in decreased E-cadherin promoter activity and subsequently decreased E-cadherin mRNA and protein expression. The data presented in this study describe a clear relationship between iron overload and decreased expression of paracellular junction genes in hepatic cells of rat and human origin.
Bilello
John P
JP
Department of Microbiology and Immunology, Milton S. Hershey Medical Center, The Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
Cable
Edward E
EE
Isom
Harriet C
HC
D000818:Animals; D016367:Baculoviridae; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics*; D003587:Cytomegalovirus / Q000235:genetics; D017931:DNA Primers; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology*; D019190:Iron Overload / Q000235:genetics* / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D012260:Ribonucleases; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
D015820:Cadherins; D017630:Connexins; D017931:DNA Primers; D007501:Iron; D012260:Ribonucleases; D001616:beta-Galactosidase