Although staining for additional mesenchymal markers check details would have strengthened the conclusions, the data are nonetheless compelling in demonstrating in the CCl4 model that hepatocytes and their derivatives do not express FSP1, type I collagen, or α-SMA and thus do not undergo EMT. Why do the authors of the two lineage tracing articles on hepatocyte EMT reach such different conclusions? Taura et al. propose that technical limitations associated with β-Gal staining yielded false-positive results in the Zeisberg

study. This hypothesis is supported by the observation that detection of β-Gal expression by immunostaining does not coincide with detection of β-Gal activity by X-gal.12 I would suggest that failure to rigorously

define EMT is another reason for the divergent findings. BIBW2992 cost Zeisberg et al. define EMT through expression of the controversial and potentially nonspecific marker FSP1 but do not examine collagen synthesis, the feature ultimately most relevant to fibrosis. Taura et al., although focused on collagen synthesis as a primary marker of EMT, also demonstrate that hepatocytes in the fibrotic liver fail to express α-SMA, a finding of key importance given the many demonstrations (including in their study) that α-SMA–positive cells make up a large percentage of fibrogenic cells. Does the work of Taura et al. lay to rest the concept of hepatocyte EMT? The answer is a qualified yes. There are caveats, including the reality that neither the genetic background of the mice nor the injury model (CCl4) accurately model human disease. Regardless, this study effectively refutes the published selleck products data that support hepatocyte EMT. Although it is still theoretically possible that hepatocyte EMT occurs in human disease,
s of evidence will be required for this to reemerge as a viable concept. Interestingly,

an exhaustive study has recently been published calling into question EMT in the kidney. Using two different epithelial cell–specific drivers, two different reporters, and two different models of renal fibrosis, Humphreys et al. find no evidence that epithelial cells of the kidney contribute to the myofibroblast population in vivo (or express FSP1).16 Like Taura and colleagues, this group suggests that nonspecific methods to detect the β-Gal reporter could have contributed to discordant findings in the literature. Thus, there is now convincing evidence that neither hepatocyte nor renal epithelial cell EMT occurs in fibrosis. Whether cholangiocyte EMT contributes to fibrosis in the liver is still an open question. Several groups, making use of both animal models and human tissue, have reported that cholangiocytes in fibrotic livers (from bile duct–ligated mice as well as humans with primary biliary cirrhosis, biliary atresia, and several other diseases) coexpress multiple epithelial and mesenchymal markers by immunostaining and are therefore likely to be undergoing EMT.