Mesenchymal-Epithelial Transition in Fibroblasts of Human Normal Lungs and Interstitial Lung Diseases.
. In passages above ten and growing very actively, we observed that some human lung fibroblasts cultured under standard conditions were transformed into a lineage of epithelial-like cells (ELC). To systematically evaluate the possible mesenchymal-epithelial transition (MET) occurrence, fibroblasts were obtained from normal lungs and also from lungs affected by idiopathic interstitial diseases. When an unusual epithelial-like phenotypic change was observed, cultured cells were characterized by confocal immunofluorescence microscopy, immunoblotting, immunocytochemistry, cytofluorometry, gelatin zymography, RT-qPCR, and hybridization in a whole-transcript human microarray. Additionally, microvesicles fraction (MVs) from ELC and fibroblasts were used to induce MET, while the microRNAs (miRNAs) contained in the MVs were identified. Pattern-gene expression of the original fibroblasts and the derived ELC revealed profound changes, upregulating characteristic epithelial-cell genes and downregulating mesenchymal genes, with a marked increase of E-cadherin, cytokeratin, and ZO-1, and the loss of expression of α-SMA, collagen type I, and Thy-1 cell surface antigen (CD90). Fibroblasts, exposed to culture media or MVs from the ELC, acquired ELC phenotype. The miRNAs in MVs shown six expressed exclusively in fibroblasts, and three only in ELC; moreover, twelve miRNAs were differentially expressed between fibroblasts and ELC, all of them but one was overexpressed in fibroblasts. These findings suggest that the MET-like process can occur in human lung fibroblasts, either from normal or diseased lungs. However, the biological implication is unclear.
['Becerril|Carina|C|', 'Montaño|Martha|M|0000-0001-7296-3365', 'Cisneros|José|J|0000-0002-4592-4464', 'Mendoza-Milla|Criselda|C|0000-0003-0304-2313', 'Pardo|Annie|A|', 'Ortiz-Quintero|Blanca|B|', 'Selman|Moisés|M|0000-0002-1022-4783', 'Ramos|Carlos|C|0000-0001-7378-6575']
D000199:Actins D000368:Aged D015415:Biomarkers D055252:Cell-Derived Microparticles D002478:Cells, Cultured D016000:Cluster Analysis D024042:Collagen Type I D015536:Down-Regulation D004847:Epithelial Cells D058750:Epithelial-Mesenchymal Transition D005347:Fibroblasts D006801:Humans D008168:Lung D017563:Lung Diseases, Interstitial D008297:Male D020778:Matrix Metalloproteinase 2 D020780:Matrix Metalloproteinase 9 D035683:MicroRNAs D010641:Phenotype D018800:Thy-1 Antigens
fibroblast epithelial-like cell microRNA E-cadherin collagen type I mesenchymal–epithelial transition α-smooth muscle actin