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Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>; 0.2\u2009mL dissolved in 100\u2009mL olive oil, 10\u2009mL\/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48\u2009h before CCl<jats:sub>4<\/jats:sub> treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl<jats:sub>4<\/jats:sub>-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl<jats:sub>4<\/jats:sub>-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl<jats:sub>4<\/jats:sub>-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. <jats:italic>In vitro<\/jats:italic> experiments showed that tumor necrosis factor-alpha (TNF-<jats:italic>\u03b1<\/jats:italic>) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-<jats:italic>\u03b1<\/jats:italic>-treated LX-2 cells. These <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.<\/jats:p>","DOI":"10.1155\/2019\/6140360","type":"journal-article","created":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T19:30:41Z","timestamp":1570735841000},"page":"1-10","source":"Crossref","is-referenced-by-count":16,"title":["Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling"],"prefix":"10.1155","volume":"2019","author":[{"given":"Weitao","family":"Ji","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Henan University, Kaifeng, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Hebei 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