Crosstalk between TGFβ and Wnt signaling pathways in the human trabecular meshwork.

Primary Open Angle Glaucoma (POAG) is an irreversible, vision-threatening disease that affects millions worldwide. The principal risk factor of POAG is increased intraocular pressure (IOP) due to pathological changes in the trabecular meshwork (TM). The TGFβ signaling pathway activator TGFβ2 and the Wnt signaling pathway inhibitor secreted frizzled-related protein 1 (sFRP1) are elevated in the POAG TM. In this study, we determined whether there is a crosstalk between the TGFβ/Smad pathway and the canonical Wnt pathway using luciferase reporter assays. Lentiviral luciferase reporter vectors for studying the TGFβ/Smad pathway or the canonical Wnt pathway were transduced into primary human non-glaucomatous TM (NTM) cells. Cells were treated with or without a combination of 5 μg/ml TGFβ2 and/or 100 ng/ml Wnt3a recombinant proteins, and luciferase levels were measured using a plate reader. We found that TGFβ2 inhibited Wnt3a-induced canonical Wnt pathway activation, while Wnt3a inhibited TGFβ2-induced TGFβ/Smad pathway activation (n = 6, p < 0.05) in 3 NTM cell strains. We also found that knocking down of Smad4 or β-catenin using siRNA in HTM5 cells transfected with similar luciferase reporter plasmids abolished the inhibitory effect of TGFβ2 and/or Wnt3a on the other pathway (n = 6). Our results suggest the existence of a cross-inhibition between the TGFβ/Smad and canonical Wnt pathways in the TM, and this cross-inhibition may be mediated by Smad4 and β-catenin.

Webber HC ，Bermudez JY ，Sethi A ，Clark AF ，Mao W ... -  《-》

GSK3β Inhibitors Inhibit TGFβ Signaling in the Human Trabecular Meshwork.

Sugali CK ，Rayana NP ，Dai J ，Harvey DH ，Dhamodaran K ，Mao W ... -  《-》

Existence of the canonical Wnt signaling pathway in the human trabecular meshwork.

Mao W ，Millar JC ，Wang WH ，Silverman SM ，Liu Y ，Wordinger RJ ，Rubin JS ，Pang IH ，Clark AF ... -  《-》

The Role of Wnt/β-Catenin Signaling and K-Cadherin in the Regulation of Intraocular Pressure.

Webber HC ，Bermudez JY ，Millar JC ，Mao W ，Clark AF ... -  《-》

TGFβ2 Induces the Formation of Cross-Linked Actin Networks (CLANs) in Human Trabecular Meshwork Cells Through the Smad and Non-Smad Dependent Pathways.

Montecchi-Palmer M ，Bermudez JY ，Webber HC ，Patel GC ，Clark AF ，Mao W ... -  《-》