Versican Mediates Mesenchymal-Epithelial Transition

Wang, Sheng; Wang, Guizhi; Pierre, David P. La; Wen, Jianping; Deng, Zhaoqun; Wong, Chung-Kwun Amy; Lee, Daniel Y.; Yang, Burton B.

doi:10.1091/mbc.e05-10-0951

Cited by 85 publications

(69 citation statements)

References 39 publications

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“…During development, MET occurs during somitogenesis, kidney development and coelomic cavity formation (25)(26)(27)(28), and a similar process plays a significant role in the repair of kidney damage (29). In tissue culture cells, MET can be induced by overexpression of the epithelial marker E-cadherin (30) or the proteoglycan versican (31). MET may also have a role in cancer progression different from that of EMT.…”

Section: Discussionmentioning

confidence: 99%

Targeted Deletion of Prkar1a Reveals a Role for Protein Kinase A in Mesenchymal-to-Epithelial Transition

et al. 2008

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Dysregulation of protein kinase A (PKA) activity, caused by loss of function mutations in PRKAR1A, is known to induce tumor formation in the inherited tumor syndrome Carney complex (CNC) and is also associated with sporadic tumors of the thyroid and adrenal. We have previously shown that Prkar1a +/À mice develop schwannomas reminiscent of those seen in CNC and that similar tumors are observed in tissuespecific knockouts (KO) of Prkar1a targeted to the neural crest. Within these tumors, we have previously described the presence of epithelial islands, although the nature of these structures was unclear. In this article, we report that these epithelial structures are derived from KO cells originating in the neural crest. Analysis of the mesenchymal marker vimentin revealed that this protein was markedly down-regulated not only from the epithelial islands, but also from the tumor as a whole, consistent with mesenchymalto-epithelial transition (MET). In vitro, Prkar1a null primary mouse embryonic fibroblasts, which display constitutive PKA signaling, also showed evidence for MET, with a loss of vimentin and up-regulation of the epithelial marker Ecadherin. Reduction of vimentin protein occurred at the posttranslational level and was rescued by proteasomal inhibition. Finally, this down-regulation of vimentin was recapitulated in the adrenal nodules of CNC patients, confirming an unexpected and previously unrecognized role for PKA in

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Section: Discussionmentioning

confidence: 99%

Targeted Deletion of Prkar1a Reveals a Role for Protein Kinase A in Mesenchymal-to-Epithelial Transition

et al. 2008

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“…Versican isoform V1 promotes cell growth, aggregation and mesenchymal-epithelial transition, whereas the V2 isoform has an inhibitory effect in these processes (Schmalfeldt et al 2000;Sheng et al 2005;Sheng et al 2006;Gu et al 2007). The V2 isoform is highly expressed in the brain, predominately in white matter, with its expression increasing in the rodent brain after post-natal day (P)18 and remaining at the high level of expression seen in the adult brain (Milev et al 1998;Oohashi et al 2002).…”

Section: Research-article2015mentioning

confidence: 99%

Correlation of Versican Expression, Accumulation, and Degradation during Embryonic Development by Quantitative Immunohistochemistry

Snyder

Washington

Birkland

et al. 2015

J Histochem Cytochem.

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SummaryVersican, a chondroitin sulfate proteoglycan, is important in embryonic development, and disruption of the versican gene is embryonically lethal in the mouse. Although several studies show that versican is increased in various organs during development, a focused quantitative study on versican expression and distribution during lung and central nervous system development in the mouse has not previously been performed. We tracked changes in versican (Vcan) gene expression and in the accumulation and degradation of versican. Vcan expression and quantitative immunohistochemistry performed from embryonic day (E) 11.5 to E15.5 showed peak Vcan expression at E13.5 in the lungs and brain. Quantitative mRNA analysis and versican immunohistochemistry showed differences in the expression of the versican isoforms in the embryonic lung and head. The expression of Vcan mRNA and accumulation of versican in tissues was complementary. Immunohistochemistry demonstrated co-localization of versican accumulation and degradation, suggesting distinct roles of versican deposition and degradation in embryogenesis. Very little versican mRNA or protein was found in the lungs of 12-to 16-week-old mice but versican accumulation was significantly increased in mice with Pseudomonas aeruginosa lung infection. These data suggest that versican plays an important role in fundamental, overlapping cellular processes in lung development and infection. (J Histochem Cytochem 63:952-967, 2015)

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“…Some ECM components such as tenascin-R, chondroitin-sulphate, versican, and vitronectin were seen underneath the basement membrane of vimentin positive basal epithelial cells (61). These components are known to occur at places where epithelial-mesenchymal transitions may take place under physiological and pathological conditions (109,110). Interestingly, such epithelial-mesenchymal transition was observed during in vitro culturing of rabbit and human limbal corneal explants (54,55).…”

Section: The Limbal Epithelial Stem Cell Nichementioning

confidence: 99%

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

et al. 2008

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The cornea is a major protective shield of the interior of the eye and represents two thirds of its refractive power. It is made up of three tissue layers that have different developmental origins: the outer, epithelial layer develops from the ectoderm overlying the lens vesicle, whereas the stroma and the endothelium have mesenchymal origin. In the adult organism, the outermost corneal epithelium is the most exposed to environmental damage, and its constant renewal is assured by the epithelial stem cells that reside in the limbus, the circular border of the cornea. Cell turnover in the stromal layer is very slow and the endothelial cells probably do not reproduce in the adult organism. However, recent experimental evidence indicates that stem cells may be found in these layers. Damage to any of the corneal layers leads to loss of transparency and low vision. Corneal limbal stem cell deficiency results in severe ocular surface disease and its treatment by transplantating ex vivo expanded limbal epithelial cells is becoming widely accepted today. Stromal and endothelial stem cells are potential tools of tissue engineering and regenerative therapies of corneal ulcers and endothelial cell loss. In the past few years, intensive research has focused on corneal stem cells aiming to improve the outcomes of the current corneal stem cell transplantation techniques. This review summarizes the current state of knowledge on corneal epithelial, stromal and endothelial stem cells. Special emphasis is placed on the molecular markers that may help to identify these cells, and the recently revealed mechanisms that could maintain their ''stemness'' or drive their differentiation. The techniques for isolating and culturing/ expanding these cells are also described. '

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Versican Mediates Mesenchymal-Epithelial Transition

Cited by 85 publications

References 39 publications

Targeted Deletion of Prkar1a Reveals a Role for Protein Kinase A in Mesenchymal-to-Epithelial Transition

Targeted Deletion of Prkar1a Reveals a Role for Protein Kinase A in Mesenchymal-to-Epithelial Transition

Correlation of Versican Expression, Accumulation, and Degradation during Embryonic Development by Quantitative Immunohistochemistry

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

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