Potential therapeutic targets for liver and kidney fibrosis. (A) Overexpression of GAS5 by lentiviruses alleviates renal fibrosis in diabetic nephropathy rat. Increased GAS5 interacts with EZH2 to the MMP9 promoter and enhances histone methylation, thus suppressing MMP9 expression. (B) MEG3 expressing adenoviral vectors are transferred into CCl4 mice. MEG3 interacts with SMO protein and suppresses Hedgehog signaling. MEG3 overexpression results in the suppression of collagen and hydroxyproline level. (C) H19 knockdown by AAV-shH19 represses EndMT. Downregulated H19 suppresses TGF-β/SMAD3 signaling and ameliorates kidney fibrosis in vivo. (D) MALAT1 is increased in CCl4 induced liver fibrosis. Knockdown of MALAT1 using Ad-shMALAT1 up-regulates miR-101b and decreases Rac1 expression. Also, α-SMA protein and collagen accumulation is decreased by knockdown of MALAT1. lncRNA, long non-coding RNA; miRNA, microRNA; CCl4, Carbon tetrachloride; AAV, Adeno associated virus; shRNA, short hairpin RNA; EndMT, Endothelial-mesenchymal transition; Ad, Adenoviral vectors.
