Aquaporin 11 insufficiency modulates kidney susceptibility to oxidative stress.

Aquaporin 11 (AQP11) is a newly described member of the protein family of transport channels. AQP11 associates with the endoplasmic reticulum (ER) and is highly expressed in proximal tubular epithelial cells in the kidney. Previously, we identified and characterized a recessive mutation of the highly conserved Cys227 to Ser227 in mouse AQP11 that caused proximal tubule (PT) injury and kidney failure in mutant mice.

Transcriptional networks in epithelial-mesenchymal transition.

Background: Epithelial-mesenchymal transition (EMT) changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis.

Methods And Findings: Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts.

A proximal activator of transcription in epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is an important mechanism for phenotypic conversion in normal development and disease states such as tissue fibrosis and metastasis. While this conversion of epithelia is under tight transcriptional control, few of the key transcriptional proteins are known. Fibroblasts produced by EMT express a gene encoding fibroblast-specific protein 1 (FSP1), which is regulated by a proximal cis-acting promoter element called fibroblast transcription site-1 (FTS-1).

Antibodies against macrophages that overlap in specificity with fibroblasts.

Background: Fibroblasts can be misidentified as macrophages because both cell types share antigens that are associated with popular antibodies targeting the monocyte/macrophage lineage. With the recent description of fibroblast-specific protein 1 (FSP1), we revisited the specificity of antibodies directed against macrophages to determine systematically which antibodies best distinguish both cell types in fibrotic tissues.

Methods: Tissue fibrosis was produced in mice carrying the GFP transgene encoding green fluorescent protein under the control of the FSP1 promoter.

The gatekeeper effect of epithelial-mesenchymal transition regulates the frequency of breast cancer metastasis.

When carcinoma cells metastasize, they change their phenotype to enhance motility. Cells making this switch selectively express S100A4, a p53-associated, calcium-binding protein known in the fibroblast literature as fibroblast-specific protein-1 (FSP1). FSP1 normally acts as a conversion signal for the local formation of tissue fibroblasts by epithelial-mesenchymal transition.