Targeting HMGB1/TLR4 axis and miR-21 by rosuvastatin: role in alleviating cholestatic liver injury in a rat model of bile duct ligation
- 89 Downloads
Many pathways are involved in the association between biliary obstruction and liver injury. We investigated the intervention influence and effect of rosuvastatin (Rvs) on the high mobility group protein 1 (HMGB1)/toll-like receptor-4 (TLR4) axis and microRNA-21 (miR-21) in cholestatic liver injury. This model was performed by ligating common bile duct of Wistar rats. Saline and Rvs were orally administrated by gastric gavages. Liver and blood samples were collected and subjected to molecular and biochemical evaluation. We found that the daily oral administration of Rvs was protective against the occurrence of cholestatic liver injury. This was evident from the results of hepatic, oxidative stress, and inflammatory biomarkers. This study also revealed the Rvs inhibitory effect on the HMGB1/TLR4 intracellular signaling axis as evidenced by decreasing the levels of nuclear factor κβ (NFκβ), tumor necrosis factor α (TNFα), and interleukin 6 (IL6) production. Furthermore, Rvs-treated group showed a significant reduction in the expression of miR-21 in comparison to the untreated group. Accordingly, rosuvastatin interference with the HMGB1/TLR4 and miR-21 expression could explain its hepatoprotective effect in cholestatic liver injury.
KeywordsCholestasis HMGB1 miR-21 Rosuvastatin TLR4
Bile duct ligation
High mobility group protein 1
Nuclear factor κβ
Polymerase chain reaction
Reactive oxygen species
Signal transducer and activator of transcription 3
Enas S. Nabih: Share in idea, design, biochemical work, and writing the manuscript.
Omnyah A. El-Kharashi: Share in idea, design, pharmacological work, and writing the manuscript.
Compliance with ethical standards
Consent for publication
The authors declare that they have no conflict of interest.
- Wang L, Li N, Lin D et al (2017) Curcumin protects against hepatic ischemia/reperfusion induced injury through inhibiting TLR4/NF-κB pathway. Oncotarget 8(39):65414–65420Google Scholar
- Xianjin DU, Xiaorong HU, Jie WEI (2013) Postconditioning with rosuvastatin reduces myocardial ischemia-reperfusion injury by inhibiting high mobility group box 1 protein expression. Exp Ther Med 7(1):117–120Google Scholar