title: Divergence of tight and adherens junction factors in alveolar epithelium in pulmonary fibrosis.
abstract: It has been proposed that an epithelial injury may be one of the multiple primary events in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The aim of this study was to characterize the tight junction and adherens junction proteins in normal human lung, IPF, cryptogenic organizing pneumonia, and asbestosis. We determined the immunohistochemical cell-specific expression of tight junction proteins claudin-1, claudin-2, claudin-3, claudin-4, claudin-5, and claudin-7, as well as 3 adherens junction proteins, E-cadherin, N-cadherin, and β-catenin. We further analyzed the expression of claudin-1, claudin-3, and claudin-4 and E-cadherin, N-cadherin, and β-catenin at the transcriptional level by quantitative real-time reverse transcriptase polymerase chain reaction. The expression levels of both tight junction and adherens junction proteins were elevated in regenerative alveolar epithelium in pulmonary fibrosis as compared with the expression of these proteins in normal alveolar epithelium. In particular, the expression levels of claudins-1 and claudin-3 were clearly elevated in all diseases. Furthermore, the amounts of adherens junction proteins messenger RNAs (mRNAs) were also all increased in pulmonary fibroses in comparison with healthy controls, with N-cadherin showing the greatest increase in mRNA levels in all diseases. However, the amounts of claudin-1, claudin-3, and claudin-4 mRNAs in fibrotic lung were similar to or even lower than those measured in the healthy controls. It is possible that the diminished capacity to produce claudin mRNAs may be one explanation for poor repair capacity of alveolar epithelial cells in IPF.
authors.affiliation: Department of Pathology, Oulu University Hospital, 90029 Oulu, Finland. elisa.lappi-blanco@ppshp.fi
authors.forename: Elisa
authors.initials: E
authors.lastname: Lappi-Blanco
authors.forename: Siri T
authors.initials: ST
authors.lastname: Lehtonen
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Heta M
authors.initials: HM
authors.lastname: Merikallio
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Riitta L
authors.initials: RL
authors.lastname: Kaarteenaho
mesh_terms: D022005:Adherens Junctions / Q000737:chemistry*; D001195:Asbestosis / Q000378:metabolism*; D015820:Cadherins / Q000032:analysis; D057167:Claudins / Q000032:analysis*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry; D011650:Pulmonary Alveoli / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000737:chemistry*
chemical_list: D015820:Cadherins; D057167:Claudins; D012333:RNA, Messenger