No EMT in lung fibrosis

In ATS 2011, a study from Dr. Brigid Hogan's laboratory suggests that mature AT2 cells appear to be capable of clonal proliferation and differentiation into Type 1 alveolar epithelial cells. However, there is no evidence that the lineage-labeled AT2 cells differentiate into mesenchymal cells using an inducible Sftpc-CreER "knock-in" mouse line in combination with a R26R-TomatoRed reporter allele. This study is against a popular hypothesis that the fibroblasts involved in the pathogenesis of IPF derive, in part, from AT2 cells, through EMT [1].

The study is consistent with other studies that did not find evidence for a contribution of EMT to kidney fibrosis [2, 3] or liver fibrosis [4, 5].


References:
[1] Barkauskas, C, et al., Lineage Tracing Of Mature Type 2 Alveolar Epithelial Cells Reveals New Insights Into Alveolar Maintenance And Repair. Am J Respir Crit Care Med 183;2011:A6347
[2] Li L, et al. Autophagy is a component of epithelial cell fate in obstructive uropathy. Am J Pathol. 2010;176(4):1767–1778.
[3] Humphreys BD, et al. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol. 2010 Jan;176(1):85-97. Epub 2009 Dec 11. PubMed PMID: 20008127; PubMed Central PMCID:PMC2797872.
[4] Scholten D, et al. Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice. Gastroenterology. 2010 Sep;139(3):987-98. Epub 2010 Jun 20. PubMed PMID: 20546735; PubMed Central PMCID: PMC2930026
[5] Taura K, et al. Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice. Hepatology. 2010 Mar;51(3):1027-36. PubMed PMID: 20052656; PubMed Central PMCID: PMC2906231.