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10 April 2018 : Laboratory Research  

Interleukin (IL)-13, Prostaglandin E2 (PGE2), and Prostacyclin 2 (PGI2) Activate Hepatic Stellate Cells via Protein kinase C (PKC) Pathway in Hepatic Fibrosis

Guode Sui1ABCDEF*, Guang Cheng1BCD, Junjun Yuan2BC, Xuena Hou2DE, Xiaochen Kong2EF, Haitao Niu3AG

DOI: 10.12659/MSM.906442

Med Sci Monit 2018; 24: LBR2134-2141


BACKGROUND: Protein kinase C (PKC), interleukin (IL)-13, prostaglandin E2 (PGE2), and prostacyclin 2 (PGI2) can all play crucial roles in pulmonary fibrosis. However, their functions remain unclear in hepatic fibrosis mediated by hepatic stellate cells (HSCs), which has been demonstrated to be related to transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF).

MATERIAL AND METHODS: All the experiments were based on LX-2 Hepatic stellate cells. The expression of TGF-β1 and PDGF were assessed by ELISA, RT-PCR, and Western blotting in human HSCs treated by IL-13, PGE2, and PGI2, respectively. At the same time, bridge assay and CCK8 assay were used to detect the cell proliferation and activity, PKC activity assay was used to test the activity of PKC, and PKC agonist and antagonist were used to verify the results obtained previously.

RESULTS: We found that IL-13, PGE2, and PGI2 significantly enhanced the expression of TGF-β1 and PDGF in human HSCs, which also clearly improved the proliferation and cell activity of HSCs. Moreover, PKC activity was significantly increased following IL-13, PGE2, and PGI2 treatments. We also found that the expression of TGF-β1 and PDGF, as well as the proliferation and cell activity of HSCs, were significantly enhanced by the PKC agonist phorbol 12-myristate 13-acetate (PMA), but suppressed by the PKC antagonist calphostin C.

CONCLUSIONS: We found that IL-13, PGE2, and PGI2 stimulated HSCs proliferation and secretion of TGF-β1 and PDGF by activating PKC, which predicted their potential roles in hepatic fibrosis.

Keywords: 16,16-Dimethylprostaglandin E2, hepatic stellate cells, Receptors, Epoprostenol, Receptors, Interleukin-13, Transforming Growth Factor beta1



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Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.938532

Med Sci Monit 2022; 28:e938532


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750