摘要
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Transforming growth factor beta (TGF13) and bone morphogenetic protein (BMP) signaling play opposing roles in epithelial-mesenchymal transition (EMT) of lens epithelial cells, a cellular process integral to the pathogenesis of fib...
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Transforming growth factor beta (TGF13) and bone morphogenetic protein (BMP) signaling play opposing roles in epithelial-mesenchymal transition (EMT) of lens epithelial cells, a cellular process integral to the pathogenesis of fibrotic cataract. We previously showed that BMP-7-induced Smad1/5 signaling blocks TGF13-induced Smad2/3signaling and EMT in rat lens epithelial cell explants. To further explore the antagonistic role of BMPs on TGF13signaling, we tested the capability of BMP-4 or newly described BMP agonists, ventromorphins, in blocking TGF13-induced lens EMT. Primary rat lens epithelial explants were treated with exogenous TGF132 alone, or in combination with BMP-4 or ventromorphins. Treatment with TGF132 induced lens epithelial cells to undergo EMT and transdifferentiate into myofibroblastic cells with upregulated a-SMA and nuclear translocation of Smad2/3 immunofluorescence. BMP-4 was able to suppress this EMT without blocking TGF132-nuclear translocation of Smad2/3. In contrast, the BMP agonists, ventromorphins, were unable to block TGF132-induced EMT, despite a transient and early ability to significantly reduce TGF132-induced nuclear translocation of Smad2/3. This intriguing disparity highlights new complexities in the responsiveness of the lens to differing BMP-related signaling. Further research is required to better understand the antagonistic relationship between TGF13 and BMPs in lens EMT leading to cataract.
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