Epithelium-mesenchyme transition

Figure 4 Possible pathophysiologic events involving innate and adaptive immunity, leading to BOS/OB. Repeat milder stimuli to the respiratory epithelium (such as for instance GER, colonization, etc.) may lead to stimulation of innate immunity ending up in neutrophilic airway inflammation, which may be reversible upon treatment with azithromycin. However, if left untreated, chronic neutrophilic inflammation and increased oxidative stress may further stimulate fibroblast activation, epithelial to mesenchymal transition, with migration of (myo)fibroblasts, leading to fibrosis of the airway wall and fibrotic plugs in the airways, typically for OB. A more severe epithelial injury (as for instance in acute rejection and CMV infection) may directiy lead to fibroblast activation and OB in a short time period, without any neutrophils being present in the airways. Abbreviations BOS, bronchiolitis obliterans syndrome OB, obliterative bronchiolitis GER, gastroesophageal reflux CMV, c) tomegalovirus.

WT1 is present in the metanephric mesenchyme before induction and is upregulated during induction. Blocking induction stops the production of WT1. WT1 is expressed at high levels during the condensation of the mesenchyme and its transition to epithelium. Its expression diminishes thereafter, except in the podocyte layer of Bowman s capsule. WT1 knockout mice do not develop kidneys. The metanephric mesenchyme from these mice cannot be induced by wild-type inducers. 

The transition from mesenchyme to epithelium involves biochemical changes in the cells and the extracellular matrix, N-CAM expression on cell surfaces disappears, replaced by L-CAM (uvomorulin). Vimentin, a characteristic cytoskeletal component of mesenchyme, disappears, and cytokeratin, characteristic of epithelia, appears. There is a decrease in collagen I extracellularly and an increase in the basement membrane components laminin and collagen IV. 

After epithelialization and the formation of the S-shaped tubule, there is still much that needs to occur in order for the nephron to function. Cells destined to form the podocyte layer of the glomerulus flatten out and lose some of the markers that characterized their earlier transition to epithelium, including c-MYC, HOX-c9, LFB-1 and LFB-3, while keeping a high level of WT1. Expression of more classical mesenchymal markers such as vimentin takes place, but the cells also keep a number of epithelial proteins such as desmosomal components. The result is a tissue that is more organized than most connective tissue but leakier than most epithelium, the optimum design for urine filtration. 

Boyd, N.L. et al.. Human embryonic stem cell-derived mesoderm-Uke epithelium transitions to mesenchymal progenitor cells. Tissue Eng Part A, 2009.15(8) 1897-907. 

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