TNIP1 alleviates hepatic ischemia/reperfusion injury via the TLR2-Myd88 pathway
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710004 (China)
Highlights: • Decreased TNIP1 was measured in hepatic I/R. • TNIP1 affected hepatocyte proliferation and apoptosis after H/R. • TNIP1 attenuated the inflammatory response in hepatocytes injured by H/R. • TNIP1 inhibited the TLR4-Myd88 signaling in hepatocytes injured by H/R. • TLR4 reversed improvement induced by TNIP1 in hepatocytes injured by H/R. Hepatic ischemia/reperfusion (I/R) injury induces oxidative stress, hepatocyte apoptosis, and release of inflammatory cytokines, which together causes liver damage and even organ dysfunction. TNF-α-induced protein 3-interacting protein 1 (TNIP1) reportedly decreases expression of genes associated with stress response and inflammation. Thus, we investigated the effects of TNIP1 on hepatic cells injury caused by hypoxia/reoxygenation (H/R). Reduced expression of TNIP1 was determined in I/R mice compared to normal mice. Then, TNIP1 transgene mice were used to determine the effects of TNIP1 on mice after treatment for I/R. In the normal transgene (NTG) group, serum liver damage markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) in I/R mice significantly increased compared to the sham-operated mice. However, in the TNIP1 transgene (TNIP1-TG) group, those levels in I/R mice were reduced than that in NTG mice. Additionally, cell viability and apoptosis in the hepatic cell line L02 were detected after H/R treatment, MTT assay showed that cell viability was inhibited after H/R treatment, but reversed after ad-TNIP1 transfection. Cell apoptosis also was inhibited after ad-TNIP1 transfection, as shown by the caspase-3 and caspase-9 levels and Bcl-2 and Bax values. Furthermore, TNIP1 overexpression also attenuated the inflammatory response of L02 cells after H/R treatment. Finally, treatment with TNIP1 reduced the elevated expression of TLR2, TLR4, and Myd88 after H/R injury, but overexpression of TLR4 reversed the effects of TNIP1. In conclusion, TNIP1 may protect H/R-induced hepatic cell injury by inhibiting the TLR4/Myd88 pathway.
- OSTI ID:
- 23125128
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 501; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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