Epithelial-to-Mesenchymal and Endothelial-to-Mesenchymal Transition

Exchange Protein Directly Activated by cAMP (epac): A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions

“…Although it is presently not known whether Epac is required for the development of cardiac hypertrophy or whether its increased expression is a result of hypertrophy, both Epac proteins are upregulated by chronic catecholamine infusion-induced hypertrophy, and only Epac1 is increased in pressure overloadinduced hypertrophy (Ulucan et al, 2007). Transforming growth factor-b 1 (TGF-b 1 ) is a central mediator of fibrogenesis and is involved in the recruitment and activation of (myo)fibroblasts, which may derive from resident mesenchymal cells, circulating fibrocytes, and/or epithelial-to-mesenchymal transition, a process in which epithelial cells transdifferentiate into mesenchymal cells (Schmierer and Hill, 2007;Biernacka et al, 2011;Nieto, 2011;Kovacic et al, 2012;Small, 2012). Loss of Epac1 by TGF-b1 accelerates the deposition of extracellular matrix proteins including collagenIa1, collagenIa2, and collagenIIIa1, and reduces Epac1-dependent migration of fibroblasts from various tissues (including heart, lung, liver, and skin), whereas overexpression of Epac1 attenuates TGF-b1-induced collagen synthesis (Yokoyama et al, 2008c), suggesting that TGF-b1-controlled Epac1 expression modulates tissue homeostasis and fibrogenesis.…”

Developmental origin and lineage plasticity of endogenous cardiac stem cells

“…As mentioned previously, the generation of morphologically and functionally different cardiac cells during embryogenesis is achieved by EMT and by mesenchymal-to-epithelial transition (MET), the reverse mechanism (Kovacic et al, 2012). Although other processes are involved, EMT and MET are essential portals to stem cell identity (Asli and Harvey, 2013) and are fundamental for cellular diversity during development and in adulthood.…”

“…Although other processes are involved, EMT and MET are essential portals to stem cell identity (Asli and Harvey, 2013) and are fundamental for cellular diversity during development and in adulthood. Interestingly, in adult tissues, EMT is not only associated with wound healing and organ repair, but also with fibrosis and cancer progression (Kalluri, 2009;Kovacic et al, 2012). In this regard, a significant difference between the embryonic and the adult environment is the role of the immune system.…”

ABCG2poslung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

“…pos MSC in vitro resulted in a mesenchymal-myofibroblast transition (2) exhibiting a similar gene profile to epithelial-mesenchymal transition in response to TGF-␤ including upregulation of SMA, collagen, and the mesenchymal transcription factor snail (17,43,51,52,54,79). Snail regulates epithelial mesenchymal transition and cell invasion downstream of TGF-␤ as well as Wnt signaling (88,102).…”