Tri-domain proteins 27 reduce inflammation and apoptosis in HK-2 cells and protect against acute kidney injury in mice.

OBJECTIVE

The kidney is one of the most commonly damaged organs in sepsis. Acute kidney injury (AKI) induced by sepsis is a clinically dangerous disease with a high mortality rate. Therefore, it is particularly important to find a way to prevent and treat sepsis-induced AKI.

MATERIALS AND METHODS

Human renal tubular epithelial cell line (HK-2) and 8-week-old C57BL/6 mice were used. Lipopolysaccharide (LPS) was used to induce HK-2 cell injury and mouse AKI. Lentiviruses overexpressing TRIM27 were constructed to increase TRIM27 expression in HK-2 cells. Then, the effects of TRIM27 on the inflammation and apoptosis of HK-2 cells were analyzed, and those of TRIM27 recombinant protein on AKI in mice was detected by immunohistochemical staining and Western blot.

RESULTS

It was found that TRIM27 overexpression reduced the expressions of inflammatory factors and signaling molecules in apoptosis-related pathways in HK-2 cells, but increased the ratio of Bcl-2 to Bax in HK-2 cells, indicating the anti-apoptotic effect of TRIM27. Toll-like receptor 4 (TLR4)/NF-κB signaling pathway is an important mechanism of LPS mediated renal injury, and TRIM27 overexpression in HK-2 cells significantly inhibited the activity of TLR4/NF-κB signaling pathway. In addition, AKI was significantly relieved in mice treated with TRIM27 recombinant.

CONCLUSIONS

TRIM27 exerts anti-inflammatory and anti-apoptotic effects by inhibiting the TLR4/NF-κB signaling pathway, which effectively alleviates LPS-induced HK-2 cell damage and mouse AKI.