Identification of LBH and SPP1 involved in hepatic stellate cell activation during liver fibrogenesis

Liver fibrosis is a pathological response driven by the activation of hepatic stellate cell (HSC). However, the mechanisms of liver fibrosis and HSC activation are complicated and far from being fully understood. We aimed to explore the candidate genes involved in HSC activation during liver fibrogenesis. Five genes (LBH, LGALS3, LOXL1, S100A6 and SPP1) were recurrent in the DEGs derived from the seven datasets. The expression of these genes gradually increased as liver fibrosis staging advanced, suggesting they might be candidate genes involved in HSC activation during hepatic fibrosis. These candidate genes were predicted to be coregulated by miRNAs such as hsa-miR-125a-5p and has-miR-125b, or by transcription factors including JUN, USF1, TP53 and TFAP2C. PPI analysis showed that LGALS3, LOXL1, S100A6 and SPP1 might interact with each other indirectly, but no interaction was found between them and LBH. The candidate genes and their interaction partners were enriched in focal adhesion, extracellular matrix organization and binding. Upregulation of LBH, S100A6 and SPP1 were further validated in TGF-β-treated LX-2 as well as in DDC or CCL4-treated mice models. Decreased LBH and SPP1 expression reduces the expression of HSC activation-related markers in TGF-β-treated LX-2. Our results indicated that LBH, LGALS3, LOXL1, S100A6 and SPP1 were candidate genes which may participate in the HSC activation during liver fibrosis.