Oxidored-nitro domain-containing protein 1 promotes liver fibrosis by activating the Wnt/β-catenin signaling pathway in vitro

Hepatic fibrosis is a characteristic of various types of chronic liver diseases, and may further develop into liver cirrhosis and liver cancer. Oxidored‑nitro domain‑containing protein 1 (NOR1) expression levels are greater in hepatitis, cirrhosis and hepatocellular carcinoma samples compared with from normal liver samples. However, the importance of NOR1 in liver fibrosis remains to be elucidated. The present study aimed to investigate the effect of NOR1 on the proliferation and matrix expression of human hepatic stellate cells (HSCs) in vitro. Additionally, the molecular mechanisms underlying the role of NOR1 in the activation of HSCs was investigated. The present study determined that transforming growth factor β1 (TGF‑β1) may induce NOR1 expression in HSCs in a dose‑dependent manner, as determined by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. NOR1‑small hairpin (sh)RNA was transfected into TGF‑β1‑treated HSCs to knock down NOR1. The MTT assay revealed that TGF‑β1‑induced cell proliferation was significantly inhibited in the NOR1‑shRNA group. In addition, NOR1 knockdown significantly inhibited TGF‑β1‑induced protein expression of fibrosis indexes, including collagen 1, 3 and α‑smooth muscle actin (α‑SMA). Subsequently, NOR1‑pcDNA3.1 was transfected into HSCs to overexpress NOR1. It was revealed that NOR1 overexpression may activate the Wnt/β‑catenin pathway in HSCs. The gain‑of function experiments demonstrated that NOR1 overexpression promoted cell proliferation and the expression of fibrosis indexes; however, these effects may be attenuated by dickkopf‑1, an inhibitor of the Wnt/β‑catenin signaling pathway. In conclusion, the present study demonstrated that NOR1 activates HSCs and contributes to liver fibrosis in vitro and this effect was achieved through the activation of the Wnt/β‑catenin pathway. Therefore, the current study may provide a novel target for the treatment of chronic liver diseases.