Epithelial-mesenchymal transition (EMT) in kidney fibrosis: Fact or fantasy?

Department of Anatomy and Developmental Biology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
The Journal of clinical investigation (Impact Factor: 13.77). 02/2011; 121(2):468-74. DOI: 10.1172/JCI44595
Source: PubMed

ABSTRACT Epithelial-mesenchymal transition (EMT) has become widely accepted as a mechanism by which injured renal tubular cells transform into mesenchymal cells that contribute to the development of fibrosis in chronic renal failure. However, an increasing number of studies raise doubts about the existence of this process in vivo. Herein, we review and summarize both sides of this debate, but it is our view that unequivocal evidence supporting EMT as an in vivo process in kidney fibrosis is lacking.

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Available from: Brigitte Kaissling, Aug 26, 2015
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    • "[26] [27]), have failed to convince part of the nephrologists community. Conflicting data emerging from fate analyses in different experimental models of renal fibrosis (reviewed in Ref. [8]) raised some doubts on the specificity of particular markers and pointed out the difficulty in detecting cells in the interstitium that express epithelial markers. The latter might be explained again by the disappearance of the epithelial phenotype after the EMT at late stages of the disease, but nonetheless intermediate states have been shown in renal, liver and cardiac fibrosis [27] [28] [29] and during the development of fibrodysplasia ossificans progressiva [30]. "
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    • "In addition, Goritz et al. (2011) recently demonstrated that a specific pericyte subtype gives rise to scar-forming stromal cells in the injured spinal cord. However, because fibroblasts in the interstitial space not only provide a scaffold for micro-tissue architecture such as nephrons and renal tubules (in the case of the kidneys), but also come into direct contact with microvessels, it is often difficult to distinguish between pericytes and tissue fibroblasts under steadystate conditions (Kriz et al., 2011). The similarities, differences, and lineage relationship between pericytes and tissue fibroblasts remain to be elucidated. "
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    Frontiers in Immunology 04/2012; 3(article 71):71. DOI:10.3389/fimmu.2012.00071
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    • "One such effect is the inhibition of EMT, although both PKA and Epac regulate features characteristic of EMT in MDCK cells (Figures 3 and 4). The contribution of EMT to tissue fibrosis in vivo is controversial (Hinz, 2010; Humphreys et al., 2010; Kriz et al., 2011; Quaggin and Kapus, 2011). Even so, the activation of Epac, potentially either Epac1 or Epac2 in different tissues, can regulate profibrotic responses, including collagen and DNA synthesis and other functional activities of fibroblasts. "
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    ABSTRACT: Fibrosis, the result of excess deposition of extracellular matrix (ECM), in particular collagen, leads to scarring and loss of function in tissues that include the heart, lung, kidney and liver. The second messenger cAMP can inhibit the formation and extent of ECM during this late phase of inflammation, but the mechanisms for these actions of cAMP and of agents that elevate tissue cAMP levels are not well understood. In this article, we review the fibrotic process and focus on two recently recognized aspects of actions of cAMP and its effector Epac (Exchange protein activated by cAMP): (a) blunting of epithelial-mesenchymal transformation (EMT) and (b) down-regulation of Epac expression by profibrotic agents (e.g. TGF-β, angiotensin II), which may promote tissue fibrosis by decreasing Epac-mediated antifibrotic actions. Pharmacological approaches that raise cAMP or blunt the decrease in Epac expression by profibrotic agents may thus be strategies to block or perhaps reverse tissue fibrosis. LINKED ARTICLES This article is part of a themed section on Novel cAMP Signalling Paradigms. To view the other articles in this section visit
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