TGFβ promotes Wnt expression during cataract development

Chong, Colin Chun Wai; Stump, Richard J.W.; Lovicu, Frank J.; McAvoy, John W.

doi:10.1016/j.exer.2008.07.018

Cited by 35 publications

(35 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ocular fibrosis, Wnt has been shown to be activated by TGF-β1 during cataract development (Chong et al, 2009) and in human orbital fibroblasts to enhance ECM production (Tan et al, 2014). Wnt inhibition suppresses the TGF-β1 inducing effects in ECM synthesis (Tan et al, 2014) and protects against diabetic retinopathy in a mouse model of induced retinal ischemia (Park et al, 2011b).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 98%

Myofibroblasts

Hinz¹

2016

Experimental Eye Research

351

341

View full text Add to dashboard Cite

Myofibroblasts are activated in response to tissue injury with the primary task to repair lost or damaged extracellular matrix. Enhanced collagen secretion and subsequent contraction - scarring - are part of the normal wound healing response and crucial to restore tissue integrity. Due to myofibroblasts ability to repair but not regenerate, accumulation of scar tissue is always associated with reduced organ performance. This is a fair price to pay by the body for not falling apart. Whereas myofibroblasts typically vanish after successful repair, dysregulation of the normal repair process can lead to persistent myofibroblast activation, for instance by chronic inflammation or mechanical stress in the tissue. Excessive repair leads to the accumulation of stiff collagenous ECM contractures - fibrosis - with dramatic consequences for organ function. The clinical need to terminate detrimental myofibroblast activities has stimulated researchers to answer a number of essential questions: where do myofibroblasts come from, what are the factors leading to their activation, how do we discriminate myofibroblasts from other cells, what is the molecular basis for their contractile activity, and how can we stop or at least control them? This article reviews the current state of the myofibroblast literature by emphasizing their role in ocular repair and fibrosis. It appears that although the eye is quite an extraordinary organ, ocular myofibroblasts behave or misbehave just like their siblings in other organs.

show abstract

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 98%

Myofibroblasts

Hinz¹

2016

Experimental Eye Research

351

341

View full text Add to dashboard Cite

show abstract

“…Ono et al have demonstrated that the downregulation of WNT/β-catenin signaling, via inhibitor of β-catenin and TCF4 (ICAT), niclosamide, or XAV939, has antitumor effects on primary cultures of human leiomyoma cells in vitro [54]. TGFβ facilitates the translocation of un-phosphorylated β-catenin from the cytoplasm to the nucleus [55] and via integration with the T-cell factor and lymphoid enhancer factor-1 (TCF/LEF1) family of transcription factors to activate WNT target gene expression [56]. In our study, we found that fucoidan treatment decreased the levels of β-catenin in both the cytoplasm and the nucleus in ELT-3 cells and abolished the TGFβ3-induced β-catenin translocation into the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Chen

Huang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGFβ). Methods: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. Results: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, α-SMA and the COL1A1 protein levels in TGFβ3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGFβ3-induced levels of p-Smad2 and p-ERK1/2, as well as β-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. Conclusion: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development.

show abstract

“…In both cases the result is to promote transdifferentiation. A report using whole rat lens cultures exposed to TGFb2 and transgenic mice over expressing TGFb1 demonstrated increased level of Wnt ligands and Frizzled receptors compared with controls; moreover, this was associated with increased accumulation of b-catenin in the nucleus of cataract forming cells and expression of aSMA/plaque formation [99].…”

Section: Tgfb: the Orchestrator Of Fibrosismentioning

confidence: 99%

The lens as a model for fibrotic disease

Eldred

Dawes

Wormstone

2011

Phil. Trans. R. Soc. B

102

View full text Add to dashboard Cite

Fibrosis affects multiple organs and is associated with hyperproliferation, cell transdifferentiation, matrix modification and contraction. It is therefore essential to discover the key drivers of fibrotic events, which in turn will facilitate the development of appropriate therapeutic strategies. The lens is an elegant experimental model to study the processes that give rise to fibrosis. The molecular and cellular organization of the lens is well defined and consequently modifications associated with fibrosis can be clearly assessed. Moreover, the avascular and non-innervated properties of the lens allow effective in vitro studies to be employed that complement in vivo systems and relate to clinical data. Using the lens as a model for fibrosis has direct relevance to millions affected by lens disorders, but also serves as a valuable experimental tool to understand fibrosis per se.

show abstract

TGFβ promotes Wnt expression during cataract development

Cited by 35 publications

References 41 publications

Myofibroblasts

Myofibroblasts

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

The lens as a model for fibrotic disease

Contact Info

Product

Resources

About