Effects of TGF-β2 on Cadherins and β-Catenin in Human Trabecular Meshwork Cells

Wecker, Thomas; Han, Hong; Börner, Juliane; Grehn, Franz; Schlunck, Günther

doi:10.1167/iovs.13-12669

Cited by 32 publications

(30 citation statements)

References 26 publications

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“…Collectively, these observations further support the interplay between HTM cell contractile hardware and ECM synthesis/deposition in the aqueous humor outflow pathway. In addition, the elicited expression of α-SMA and ECM proteins by TGFβ2 suggests transdifferentiation of HTM cells into myofibroblast-like cells expressing fibrogenic and fibroblast-like markers, as recently reported by others3132.…”

Section: Discussionsupporting

confidence: 74%

TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor

Torrejon

Papke

Halman

et al. 2016

Sci Rep

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Members of the transforming growth factor beta (TGFβ) cytokine family have long been associated with affecting several cellular functions, including cell proliferation, differentiation and extracellular matrix (ECM) turnover. Of particular interest to this work, TGFβ2 has been linked to most types of glaucomas as a potential fibrotic agent that can cause elevation of intraocular pressure (IOP). Given that the trabecular meshwork (TM) provides most of aqueous humor outflow resistance in the eye, an in vitro bioengineered human TM (HTM) model has been created and validated by analyzing effects of TGFβ2 on transcellular pressure changes and outflow facility. These changes were correlated with several biological alterations induced by this cytokine, including ECM production and overexpression of HTM-marker myocillin. Furthermore, this TM model has been used to extend current knowledge of gene expression of cytokines involved in TGFβ-induced ECM turnover over time. In particular, the ability for a ROCK-inhibitor to diminish the effect of TGFβ on TM was demonstrated. This work supports the notion that anti-fibrotic activities of ROCK-inhibitors could counteract the elevation of IOP and increased strain observed in glaucomatous TM.

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Section: Discussionsupporting

confidence: 74%

TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor

Torrejon

Papke

Halman

et al. 2016

Sci Rep

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“…48,52 The increased expression of a-SMA and ECM proteins caused by Dex suggests transdifferentiation of HTM cells into myofibroblast-like cells expressing fibrogenic and fibroblast-like markers, as recently reported by others. 48,53 Furthermore, fibronectin is reported to induce a-SMA expression via positive feedback, 54 thus, the increased fibronectin expression might facilitate fibrogenic changes of HTM cells. Inhibition of ATX was associated with a significant decrease in Dex-induced lysoPLD activity in conditioned media, while neither an LPA receptor antagonist nor a ROCK inhibitor showed any effect (Fig.…”

Section: Cytoskeletal and Ecm Changes Associated With Atx In Tm Cellsmentioning

confidence: 99%

Role of the Autotaxin-LPA Pathway in Dexamethasone-Induced Fibrotic Responses and Extracellular Matrix Production in Human Trabecular Meshwork Cells

Honjo

Igarashi

Nishida

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…This complex formation at the promoter region activates gene transcription and turns on the expression of ECM molecules such as TGM2, LOX and FN (Medina-Ortiz et al, 2013; Sethi et al, 2011; Tovar-Vidales et al, 2011). Alternatively, activation of the non-Smad pathways such as JNK, P38, or ERK 1/2 alter the expression of cell adhesion molecules (Wecker et al, 2013). …”

Section: Glaucomamentioning

confidence: 99%

Cross-linked actin networks (CLANs) in glaucoma

Bermudez

Montecchi-Palmer

Mao

et al. 2017

Experimental Eye Research

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One of the major causes of decreased vision, irreversible vision loss and blindness worldwide is glaucoma. Increased intraocular pressure (IOP) is a major risk factor associated with glaucoma and its molecular mechanisms are not fully understood. The trabecular meshwork (TM) is the primary site of injury in glaucoma, and its dysfunction results in elevated IOP. The glaucomatous TM has increased extracellular matrix deposition as well as cytoskeletal rearrangements referred to as cross-linked actin networks (CLANs) that consist of dome like structures consisting of hubs and spokes. CLANs are thought to play a role in increased aqueous humor outflow resistance and increased IOP by creating stiffer TM cells and tissue. CLANs are inducible by glucocorticoids (GCs) and TGFβ2 in confluent TM cells and TM tissues. The signaling pathways of these induction agents give insight into the possible mechanisms of CLAN formation, but to date, the mechanism of CLANs regulation by these pathways has yet to be determined. Understanding the role CLANs play in IOP elevation and their mechanisms of induction and regulation may lead to novel treatment options to help prevent or intervene in glaucomatous damage to the trabecular meshwork.

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Effects of TGF-β2 on Cadherins and β-Catenin in Human Trabecular Meshwork Cells

Cited by 32 publications

References 26 publications

TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor

TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor

Role of the Autotaxin-LPA Pathway in Dexamethasone-Induced Fibrotic Responses and Extracellular Matrix Production in Human Trabecular Meshwork Cells

Cross-linked actin networks (CLANs) in glaucoma

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