Smad7 alleviates glomerular mesangial cell proliferation via the ROS-NF-κB pathway
Abstract Objective The aim of this study was to demonstrate that altered gene expression of Smad7regulated NF-κB expression and ROS production on Ang II (Angiotensin II)-induced rat glomerular mesangial cell (GMC) proliferation. Methods pAdTrack-CMV-Smad7 was transduced into rat GMC by adeno-transduction using an ADV (adenovirus)-mediated vector in vivo. Diphenylene iodonium chloride (DPI) pre-treated GMC, and blocked ROS generation as determined by DCFH-DA method. Altered expressions of IκBα and p65 were monitored by Western blot analysis and immunofluorescence. GMC proliferation was tested by the Cell Counting Kit-8 assay. Apoptosis of GMC was detected by flow cytometric analysis. Results Over-expression of Smad7 dampened the ability of Ang II to promote ROS synthesis and inhibited the ability of Ang II to decrease functional expression of IκBα. Moreover, Smad7 increased nuclear IκBα expression. Smad7 did not significantly influence the capacity of Ang II to increase protein expression of NF-κB p65. However, immunofluorescence analysis showed that Smad7 reduced nuclear NF-κB p65 level. Further, over-expression of Smad7 promoted GMC apoptosis by inhibiting NF-κB activation, which alleviated the Ang II-promoted proliferation of GMC. Conclusions Smad7 influenced NF-κB expression by regulating ROS generation, and induced GMC apoptosis to counter the Ang II-promoted proliferation. Highlights Smad7 alleviates glomerular mesangial cell proliferation. Smad7 regulates NF-κB through a mechanism involving ROS production. Smad7 affects not only cell proliferation but also cell apoptosis.
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