Effect of SHP2 inhibition on hepatic stellate cell transcriptome.

Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis. Primary human hepatic stellate cells were treated with PDGF or PDGF + SHP2 inhibitor. RNA was purified and submitted for sequencing to Mayo Clinic Genomics Core. After applying the filters FDR>0.05, Log2(FC)>1 and RPKM>15, we ended up with nearly 300 genes differentially regulated between the two conditions. Ingenuity Pathway Analysis revealed that Ostheoarthritis was the first pathway to be differentially regulated. From this pathway, REDD1 (DDIT4 transcript), an mTOR inhibitor, was further explored, especially in the context of extracellular vesicle release. Primary human hepatic stellate cells were treated with PDGF or PDGF + SHP099 for 48 hours.