Connective tissue growth factor induces tubular epithelial to mesenchymal transition through the activation of canonical Wnt signaling<i>in vitro</i>

Yang, Zhao; Sun, Lina; Nie, Huibin; Liu, Haiying; Liu, Gang; Guan, Guangju

doi:10.3109/0886022x.2014.967699

Cited by 12 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar situations occurred with IL7R vs IL1R, and THBS1 vs THBD, although the pattern of the joint involvement of the overall IL, IGF, and TGFβ families is in agreement with their cooperative role as EMT inducers ( 68 ). The considerable upregulation by ethanol of CTGF is also in agreement with its well known role in EMT ( 69 ), but the concerted upregulation of IGFBPs 2, 3 and 4 is more intriguing, considering the paucity of studies and some conflicting evidence for their pro- versus anti-EMT effects ( 70 – 72 ). The upregulation of IGFR2 is in agreement with the higher levels observed in breast cancer tissue ( 73 ).…”

Section: Discussionsupporting

confidence: 54%

Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features

Gelfand

Vernet

Bruhn

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Alcoholism is associated with breast cancer incidence and progression, and moderate chronic consumption of ethanol is a risk factor. The mechanisms involved in alcohol's oncogenic effects are unknown, but it has been speculated that they may be mediated by acetaldehyde. We used the immortalized normal human epithelial breast cell line MCF-12A to determine whether short- or long-term exposure to ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations, induces their oncogenic transformation and/or the acquisition of epithelial mesenchymal transition (EMT). Cultures of MCF-12A cells were incubated with 25 mM ethanol or 2.5 mM acetaldehyde for 1 week, or with lower concentrations (1.0–2.5 mM for ethanol, 1.0 mM for acetaldehyde) for 4 weeks. In the 4-week incubation, cells were also tested for anchorage-independence, including isolation of soft agar selected cells (SASC) from the 2.5 mM ethanol incubations. Cells were analyzed by immunocytofluorescence, flow cytometry, western blotting, DNA microarrays, RT/PCR, and assays for miRs. We found that short-term exposure to ethanol, but not, in general, to acetaldehyde, was associated with transcriptional upregulation of the metallothionein family genes, alcohol metabolism genes, and genes suggesting the initiation of EMT, but without related phenotypic changes. Long-term exposure to the lower concentrations of ethanol or acetaldehyde induced frank EMT changes in the monolayer cultures and in SASC as demonstrated by changes in cellular phenotype, mRNA expression, and microRNA expression. This suggests that low concentrations of ethanol, with little or no mediation by acetaldehyde, induce EMT and some traits of oncogenic transformation such as anchorage-independence in normal breast epithelial cells.

show abstract

Section: Discussionsupporting

confidence: 54%

Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features

Gelfand

Vernet

Bruhn

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…This point warrants further investigation. Furthermore, recent studies have reported that CTGF itself induces EMT in renal cells (46,47). If this is also the case in retinal cells, we can assume that CTGF and Snail form a positive loop, resulting in a vicious circle of the development of vitreoretinal disorders.…”

Section: Discussionmentioning

confidence: 91%

High glucose-induced epithelial-mesenchymal transition contributes to the upregulation of fibrogenic factors in retinal pigment epithelial cells

Che

Zhou

Lan

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

It has been reported that epithelial-mesenchymal transition (EMT) mediates multiple physiological and pathological processes. However, the occurrence and the pathogenic role of high glucose-induced EMT in retinal pigment epithelial cells (RPE cells) is unknown. The aim of this study was to examine the effects of high glucose on EMT in RPE cells. Cultured RPE cells were exposed to 25 mM D-glucose. A vector encoding the Snail gene and siRNA targeting Snail (Snail siRNA) were transfected into the cells to induce the overexpression or silencing of Snail, respectively. AKT and extracellular signal-regulated kinase (ERK) inhibitors were used to block the activation of AKT and ERK, respectively. The levels of EMT markers, fibrogenic factors, phosphorylated ERK and phosphorylated AKT were determined by western blot analysis and immunofluorescence staining. Cell migration was evaluated by wound healing assay. Our results revealed that high glucose elevated the expression of the key EMT transcriptional factor, Snail, and that of other mesenchymal makers, and promoted cell migration. Moreover, the overexpression of Snail elevated the levels of fibronectin and connective tissue growth factor (CTGF), whereas the silencing of Snail decreased the expression of fibronectin and CTGF induced by high glucose in the cells. Mechanistically, the AKT inhibitor (AKT inhibitor IV) and ERK inhibitor (U0126) significantly decreased the expression of Snail, as well as the levels of fibronectin and CTGF which were induced by high glucose. On the whole, and to the best of our knowedge, the present study is the first to demonstrate the upregulation of mesenchymal markers in RPE cells induced by high glucose, and suggest that mesenchymal transition may be involved in the pathological processes of retinal diseases.

show abstract

“…Hydrogen sulfide inhibits TGF-β1-induced EMT via Wnt/β-catenin pathway ( Guo et al, 2016 ). CTGF induces tubular EMT through the activation of canonical Wnt signaling ( Yang et al, 2015 ). Chronic cadmium exposure induces activation of the Wnt pathway and upregulation of EMT markers in mouse kidney ( Chakraborty et al, 2010 ).…”

Section: New Signals That Mediate Pemt and Subsequent Renal Fibroblasmentioning

confidence: 99%

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

2020

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT) is described as the process in which injured renal tubular epithelial cells undergo a phenotype change, acquiring mesenchymal characteristics and morphing into fibroblasts. Initially, it was widely thought of as a critical mechanism of fibrogenesis underlying chronic kidney disease. However, evidence that renal tubular epithelial cells can cross the basement membrane and become fibroblasts in the renal interstitium is rare, leading to debate about the existence of EMT. Recent research has demonstrated that after injury, renal tubular epithelial cells acquire mesenchymal characteristics and the ability to produce a variety of profibrotic factors and cytokines, but remain attached to the basement membrane. On this basis, a new concept of "partial epithelial-mesenchymal transition (pEMT)" was proposed to explain the contribution of renal epithelial cells to renal fibrogenesis. In this review, we discuss the concept of pEMT and the most recent findings related to this process, including cell cycle arrest, metabolic alternation of epithelial cells, infiltration of immune cells, epigenetic regulation as well as the novel signaling pathways that mediate this disturbed epithelial-mesenchymal communication. A deeper understanding of the role and the mechanism of pEMT may help in developing novel therapies to prevent and halt fibrosis in kidney disease.

show abstract

Connective tissue growth factor induces tubular epithelial to mesenchymal transition through the activation of canonical Wnt signalingin vitro

Cited by 12 publications

References 27 publications

Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features

Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features

High glucose-induced epithelial-mesenchymal transition contributes to the upregulation of fibrogenic factors in retinal pigment epithelial cells

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

Contact Info

Product

Resources

About