Elasticity-dependent modulation of XXXX responses in @entity1 trabecular meshwork cells.

@entity1 @entity2289 @entity5732 @entity1538 @entity3963 @entity6099 @entity726 @entity1970 @entity2306 @entity2533 @entity2975 @entity10412 @entity6474 @entity14877
PURPOSE: To gain further insight into a possible role of biomechanical cues in @entity726 , the authors assessed the influence of extracellular matrix (ECM) elasticity on @entity6474 -induced changes in trabecular meshwork (TM) cells. METHODS: @entity1 TM cells derived from donor cornea rings were plated on rigid collagen-coated tissue culture plastic or @entity2975 gels of different elasticity and treated with vehicle or @entity6474 . Activation of @entity14877 , @entity3963 , and AKT signaling and expression of @entity1970 and @entity2289 proteins were assessed by Western blot analysis. Subcellular localization of @entity1970 was determined by confocal immunofluorescence microscopy. Transcription of collagen-I, -IV, and -VI, @entity1970 , @entity2289 , fibronectin, @entity6099 , cochlin, and MGP-1 was studied by RT-qPCR. The contribution of non-Smad signaling pathways to @entity2533 -induced @entity1970 and @entity2289 expression was assessed using the small molecule inhibitors @entity5732 and @entity2306 . RESULTS: @entity6474 -induced activation of @entity14877 , @entity3963 , and AKT signaling as well as expression of collagen-1, @entity1970 , fibulin, and MGP-1 were attenuated with increasing elasticity. In contrast, @entity6474 -induced collagen-6, fibronectin, @entity2289 , and cochlin expression were enhanced on elastic substrates. The MEK-inhibitor @entity5732 blocked @entity2533 -induced @entity2289 expression, whereas @entity1970 expression was enhanced. @entity10412 inhibition with @entity2306 reduced @entity1970 expression. CONCLUSIONS: ECM elasticity modulates @entity2533 -induced signaling and protein expression in @entity1 TM cells. Non-Smad signaling contributes to @entity2533 -induced alterations. Increasing ECM elasticity in vitro promotes protein expression patterns reminiscent of patterns reported in primary @entity1538 . Therefore, changes in TM elasticity and mechanical load may have a significant role in primary @entity1538 .
