The contribution of epithelial-mesenchymal transition to renal fibrosis differs among kidney disease models.

The impact of the epithelial-mesenchymal transition (EMT) to the formation of renal fibrosis has been debated in several lineage-tracing studies, with conflicting findings. Such disparities may have arisen from varying experimental conditions such as different disease models, the mouse strain, and type of genetic alteration used. In order to determine the contribution of these factors to EMT, we generated four kidney disease models in several mouse strains genetically modified to express enhanced green fluorescence protein (EGFP) in cortical tubular epithelial cells under the control of the γ-glutamyl transpeptidase promoter. Using this approach, the EMT was visible and quantifiable based on a count of EGFP-positive interstitial cells in the fibrotic kidney sections of the four renal disease models found to be either EMT-prone or -resistant. The EMT-prone models consisted of unilateral ureteral obstruction and ischemic nephropathy in SJL mice. The EMT-resistant models consisted of ureteral obstruction in C57B/6 and F1(C57B/6 × SJL) mice, adriamycin nephrosis in 129 mice, and nephrotoxic serum nephritis in SJL mice. Analyses of these renal disease models suggest the emergence of EMT-derived fibroblasts arises in a disease-specific and strain-dependent manner. Thus, when considering molecular mechanisms and involvement of the EMT in renal fibrosis, it is important to take into account the experimental conditions, particularly the mouse strain and type of disease model.