Different mode of action of lncRNAs in liver and kidney fibrosis. (A) Up-regulated H19 interacts with ZEB1 and inhibits its binding to the EpCAM promoter region, thus blockage ZEB1 from repression EpCAM transcription in cholestatic liver fibrosis. (B) Lnc-LFAR1 interacts with Smad2/3 proteins and accelerates the binding of these factors to the promoter regions of target genes in liver fibrosis. (C) LncRNAs interact with miRNA in liver fibrosis. Up-regulated lncRNAs affect target gene expression by functioning as competing with the miRNAs. Down-regulated lncRNAs could be increase miRNA and decrease anti-fibrogenic gene expression. (D) ARAP1-AS2 is up-regulated in db/db diabetic mice. ARAP1-AS2 binds ARAP1 and inhibits EGFR ubiquitination. Thus, EGFR stimulates TGF-β downstream signaling and increases collagen I/IV. (E) In unilateral ureteral obstruction (UUO) renal fibrosis model, lnc-TSI is decreased. lnc-TSI inhibits SMAD3 phosphorylation by disrupting the interaction with SMAD3 and TGF-β-R. Decreased lnc-TSI in tubulointerstitial fibrosis upregulates TGF-β downstream signaling. (F) LncRNAs bind to miRNA in kidney fibrosis. Increased lncRNAs regulate profibrogenic genes by sponging of miRNAs. GAS5 and lncRNA4474 are decreased in renal fibrosis, accompanied by up-regulation of miRNA and down-regulation of anti-fibrogenic genes.
