Novel protein C6ORF120 promotes liver fibrosis by activating hepatic stellate cells through the PI3K/Akt/mTOR pathway

Xin Wang; Hui Liu; Yuqi Wang; Peng Wang; Yunyun Yi; Yingying Lin; Xin Li

doi:10.1111/jgh.16538

Novel protein C6ORF120 promotes liver fibrosis by activating hepatic stellate cells through the PI3K/Akt/mTOR pathway

J Gastroenterol Hepatol. 2024 Mar 24. doi: 10.1111/jgh.16538. Online ahead of print.

Authors

Xin Wang¹, Hui Liu², Yuqi Wang³, Peng Wang³, Yunyun Yi³, Yingying Lin¹, Xin Li^{1

3}

Affiliations

¹ Department of Center of Integrated Traditional Chinese and Western Medicine, Peking University Ditan Teaching Hospital, Beijing, China.
² Department of Center of Infectious Disease, Beijing Ditan Hospital; Capital Medical University, Beijing, China.
³ Department of Center of Integrated Traditional Chinese and Western Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

PMID: 38523410
DOI: 10.1111/jgh.16538

Abstract

Background and aim: The role of C6ORF120 in promoting CCL4-induced hepatic fibrosis and its possible mechanisms were explored in C6orf120 knockout rats (C6orf120^-/-) and LX-2 cells (a type of human hepatic stellate cell line).

Methods: In vivo experiments, wild-type and C6orf120^-/- rats were used to investigate the function of C6ORF120. In the in vitro experiments, C6ORF120 recombinant protein (rC6ORF120) at a concentration of 200 ng/mL was used to stimulate LX-2 cells. Sirius Red staining, Masson staining, western blotting, polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to explore fibrosis-associated factors.

Results: C6orf120^-/- rats showed mild fibrosis and liver injury in the CCL4-induced liver fibrosis model. Furthermore, RNA-seq revealed that C6orf120^-/- rats had less extracellular matrix deposition and activated stellate cells. Consistent with the in vivo, the rC6ORF120 induced LX-2 cell activation. Moreover, mechanistic studies revealed that the p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR levels were significantly elevated and LY294002 (a PI3K/Akt/mTOR typical pathway inhibitor) reversed the function of C6ORF120 in activating LX-2 cells.

Conclusion: C6ORF120 could activate hepatic stellate cells and promote hepatic fibrosis via the PI3K/Akt/mTOR signaling pathway.

Keywords: C6ORF120; PI3K/Akt/mTOR signaling pathway; hepatic stellate cell; liver fibrosis.

Abstract

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