NEK2 alleviates renal inflammation and apoptosis in sepsis- associated acute kidney injury by activating the MAPK signaling pathway

Immunobiology. 2026 Jun 1;231(3):153196. doi: 10.1016/j.imbio.2026.153196. Online ahead of print.

ABSTRACT

Sepsis-associated acute kidney injury (S-AKI) has a high mortality rate. Its pathogenesis involves excessive inflammation and cell apoptosis. NEK2 is implicated in the inflammatory process, but its specific role in S-AKI remains unclear. This study investigates the function and mechanism of NEK2 in S-AKI by using a cecal ligation and puncture (CLP)-induced septic mouse model and LPS-treated HK-2 cells to simulate kidney injury in vitro. We found NEK2 was upregulated in the renal cortex of S-AKI mice. Pathological staining indicated vacuolar degeneration and interstitial inflammatory cell infiltration in the kidney, along with local thickening of the basement membrane. Knockdown of NEK2 alleviated kidney damage, reduced serum BUN and Scr levels, and suppressed renal cell apoptosis, as evidenced by decreased Bax and cleaved caspase-3 and increased Bcl2. Furthermore, NEK2 knockdown decreased TNF-α, IL-6, and IL-1β levels in the renal cortex of S-AKI mice. Consistent in vitro results confirmed that NEK2 interference inhibited inflammation and apoptosis. Additionally, we found that NEK2 interacted with ERK2 and increased the levels of p-ERK1/2, exacerbating kidney damage. The protective effect of NEK2 knockdown was counteracted by a p-ERK1/2 agonist. In conclusion, NEK2 is upregulated in S-AKI mice and promotes kidney injury. Mechanistically, NEK2 binds to ERK2, activating the ERK1/2 signaling pathway, which exacerbates cellular inflammation and apoptosis. These findings provide a theoretical basis for understanding S-AKI pathogenesis and hold promise for developing novel therapeutic strategies for patients with this condition.

PMID:42275702 | DOI:10.1016/j.imbio.2026.153196