Coordinated Regulation Of Palladin And Alpha-Smooth Muscle Actin By Transforming Growth Factor-Beta In Human Corneal Fibroblasts
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE(2016)
摘要
PURPOSE. To investigate the role of palladin in the cornea, we examined expression of this actin assembly-related protein in normal, diseased, or injured corneal tissue as well as in cultured corneal fibroblasts.METHODS. Expression of palladin and alpha-smooth muscle actin (alpha-SMA) in the rat cornea with an incision wound, in the normal and diseased human cornea, and in cultured human corneal fibroblasts was examined by immunofluorescence or immunoblot analysis.RESULTS. The expression of both palladin and alpha-SMA was detected at the lesion site during wound healing in the rat cornea. Whereas neither palladin nor alpha-SMA was detected in the normal human cornea, the colocalization of both proteins was detected in diseased human corneas with underlying conditions characterized by the presence of fibrosis. The expression of both palladin and alpha-SMA in cultured human corneal fibroblasts was increased by transforming growth factor-beta (TUGF-beta) in a manner sensitive to inhibition by blockers of Smad or mitogen-activated protein kinase (MAPK) signaling. Finally, RNA interference-mediated depletion of palladin attenuated the TGF-beta-induced upregulation of alpha-SMA expression in human corneal fibroblasts as well as TGF-beta-induced collagen gel contraction mediated by these cells.CONCLUSIONS. Palladin is expressed in the rat and human cornea in association with scar formation. Expression of palladin in human corneal fibroblasts is increased by TGF-beta in a manner dependent on Smad and MAPK signaling and is required for the TGF-j-induced upregulation of alpha-SMA.
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关键词
palladin, TGFb, alpha-smooth muscle actin, corneal fibroblasts
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