Fig. 6

Drugs targeting the fibrosis process in NASH. Chronic hepatocyte injury induces the activation of hepatic stellate cells (HSCs) and the recruits of immune cells, which result in the deposition and cross-linking of collagens in the extracellular matrix and eventually progress to fibrosis. TGFβ/SMAD signaling, a key pathway in the development of liver fibrosis and inflammation, activates Smad pathway and no-Smad pathway. Activation of TGF-β signaling with OSM exposure drives a cooperative STAT3/SMAD3 gene transcriptional program. OSMR/JAK-mediated STAT3 signaling promotes liver fibrosis and HSCs activation by phosphorylation of SMAD3, resulting in transcriptional activation of select STAT3/SMAD3 targets. Antagonists are indicated with a red inhibitor. Drugs at different clinical stages are as indicated. Drugs at different clinical stages are indicated in different colors. Created with BioRender. Ncst ASO nicastrin antisense oligonucleotide, CCR2/5 C-C chemokine receptor 2/5, MoMF monocyte-derived macrophages, TGF-β transforming growth factor-β, LOXL2 lysyl oxidase-like 2, HSC hepatic stellate cell, OSM oncostatin M, IL-11 interleukin-11, IL-11R IL-11 receptor, GP130 glycoprotein 130, JNK c-Jun N-terminal kinase, STAT3 signal transducer and activator of transcription 3, hsp47 Heat shock protein-47