Knockdown of elF3a inhibits TGF-β1-induced extracellular matrix protein expression in keloid fibroblasts

Keloid formation is characterized by hyperproliferation of secretory and responsive keloid fibroblasts (KFs) and overproduction of extracellular matrix (ECM). Eukaryotic translation initiation factor 3 subunit A (eIF3a) one of the core subunits of the translation initiation complex, eIF3, has previously been reported to possess an anti-fibrogenic effect. However, the role of eIF3a in keloid formation has not yet been investigated. Therefore, the present study examined the effect of eIF3a on transforming growth factor-1 (TGF-1)-mediated ECM expression in KFs. The expression levels of eIF3a in human keloid tissues was evaluated using reverse transcription-quantitative polymerase chain reaction and western blotting. KFs were incubated with siRNA-eIF3a or siRNA-mock for 48 h. The cells were then treated with TGF-1 (10 ng/ml) for 72 h. Cell proliferation was evaluated using the CCK-8 assay. The expression levels of -SMA, collagen type I, TGF- receptor I (RI), TGF- RII, phosphorylated (p)-mothers against decapentaplegic homolog (Smad2), Smad2, p-Smad3 and Smad3 were detected western blotting. The present study identified significant upregulation of eIF3a mRNA and protein and in human keloid tissues compared with in normal tissues. Knockdown of eIF3a inhibited KF proliferation induced by TGF-1. In addition, eIF3a silencing significantly suppressed the TGF-1-induced expression of -smooth muscle actin, collagen I, TGF- RI and TGF- RII in KFs. Furthermore, eIF3a silencing inhibited the phosphorylation levels of Smad2 and Smad3 in TGF-1-induced KFs. To the best of our knowledge, the current study is the first to demonstrate that siRNA-eIF3a inhibits the expression ECM proteins via the TGF-1/Smad signaling pathway in KFs. Therefore, eIF3a may be a potential, novel target for treatment of keloids.