MicroRNAs in liver fibrosis: Focusing on the interaction with hedgehog signaling

Figure 1 MicroRNAs regulating hedgehog signaling. In the absence of hedgehog (HH) ligands, patched (PTCH), one of HH receptor, suppresses smoothened (SMO). The suppressor of fused (SUFU) proteins bind and induce the ubiquitination of the GLI-Kruppel (Gli) family including Gli1, Gli2, and Gli3. NUMB protein also inhibits the processing of Gli proteins to the activator forms (Gli-A). When HH ligands bind to the PTCH, SMO is released from the PTCH’s repression and activates Glis by promoting the dissociation of Glis from SUFU and inhibiting the degradation of Gli. Gli-A translocates into the nucleus and contributes to the expression of HH-target genes. The promoter region of PTCH1 is hypermethylated in activated hepatic stellate cells by DNA methyltransferase 1 (DNMT1). The HH-interacting protein (HHIP) is a negative regulator of HH signaling by antagonizing the HH ligands. Here, we shows the interrelationships of microRNAs (miRNAs) with HH signaling-associated components. The functions of miRNAs in yellow box have been proved in liver fibrosis, and the miRNAs in white box are reported to interact with HH signaling in the experimental models for other organs, besides liver. CDON: CAM-related/downregulated by oncogenes; BOC: Brother of CDO; GAS1: Growth arrest-specific 1.