title: Mesothelial differentiation as reflected by differential gene expression.
abstract: Human mesothelial cells obtained from benign effusions retain their proliferative capacity and grow uniformly either with a fibroblastic or epithelioid morphology in vitro. These cultures therefore provide a model for the process of mesothelial differentiation in vivo. To study this differentiation, we isolated differentially expressed genes obtained by suppression subtractive hybridization. Of the nine genes found to be overexpressed in fibroblastic mesothelial cells, three are matrix-associated (integrin alpha5, collagen binding protein 2, human cartilage glycoprotein 39), whereas the others are associated with a proliferative cell type (14-3-3 epsilon, plexin B2, N33, and three genes encoding ribosomal elements). Seven of the eight genes upregulated in the epithelioid phenotype are related rather to specialized functions, such as metabolism (aldose reductase, lecithin:cholesterol acyltransferase, ATPase 6), cytoskeletal composition (cytokeratins 7 and 8), and regulation of differentiation (granulin, annexin II). Immunohistochemistry with available antibodies to six of the differentially expressed gene products confirmed the differences also in pleural tissues, where submesothelial cells displayed the fibroblastic markers, whereas surface cells displayed the epithelioid markers. In summary, this approach revealed a pattern of genes coordinately regulated during mesothelial differentiation and suggests that mesothelium may regenerate also by recruiting cells from the submesothelial layer. Some of the gene products may also be useful markers for differentiation and activation in serosal tissues.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Sun
authors.forename: Miklós
authors.initials: M
authors.lastname: Gulyás
authors.forename: Anders
authors.initials: A
authors.lastname: Hjerpe
mesh_terms: D048948:14-3-3 Proteins; D054392:Adipokines; D000449:Aldehyde Reductase / Q000235:genetics; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D039482:Integrin alpha5 / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D053552:Keratin-7; D007633:Keratins / Q000235:genetics; D037102:Lectins; D009419:Nerve Tissue Proteins / Q000235:genetics; D010996:Pleural Effusion / Q000166:cytology* / Q000235:genetics; D000077153:Progranulins; D011956:Receptors, Cell Surface / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D048948:14-3-3 Proteins; D054392:Adipokines; C084533:CHI3L1 protein, human; D002352:Carrier Proteins; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D039482:Integrin alpha5; D036341:Intercellular Signaling Peptides and Proteins; C507497:KRT7 protein, human; D053552:Keratin-7; D037102:Lectins; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D000077153:Progranulins; D011956:Receptors, Cell Surface; C046289:colligin; D007633:Keratins; D000449:Aldehyde Reductase; D014446:Tyrosine 3-Monooxygenase