Sepsis is a complex clinical syndrome with high incidence and mortality. Acute lung injury (ALI) is a common complication of sepsis. At present, there is no effective therapeutic strategy to treat ALI. The SET domain–containing histone methyltransferase Wolf–Hirschhorn syndrome candidate 1 (WHSC1) regulates cancer progression, while its role in sepsis-induced ALI remains unclear. Thus, this study aimed to study the effect of WHSC1 on sepsis-induced ALI and to explore the potential mechanism of action. In the study, LPS treatment induced lung injury. WHSC1 was highly expressed in LPS-induced ALI. Knockdown of WHSC1 attenuated LPS-induced ALI and pyroptosis in vivo. Besides, knockdown of WHSC1 attenuated LPS-induced alveolar macrophage pyroptosis in vitro. Furthermore, NIMA-related kinase-7 (NEK7) expression could be regulated by WHSC1, and NEK7 bound to NLRP3 in alveolar macrophages. Moreover, WHSC1 regulated alveolar macrophage pyroptosis through modulating NEK7-mediated NLRP3 inflammasome activation. In conclusion, WHSC1 was highly expressed in LPS-induced ALI. WHSC1 facilitated alveolar macrophage pyroptosis in sepsis-induced ALI through NEK7-mediated NLRP3 inflammasome activation. WHSC1 may be a valuable target for the therapy of sepsis-induced ALI.

脓毒症是一种复杂的临床综合征，发病率和死亡率较高。急性肺损伤（ALI）是脓毒症的常见并发症。目前，尚无有效的治疗策略来治疗ALI。含有 SET 结构域的组蛋白甲基转移酶 Wolf-Hirschhorn 综合征候选 1 (WHSC1) 调节癌症进展，但其在脓毒症诱发的 ALI 中的作用仍不清楚。因此，本研究旨在研究WHSC1对脓毒症引起的ALI的影响并探讨潜在的作用机制。在该研究中，LPS 治疗引起肺损伤。 WHSC1 在 LPS 诱导的 ALI 中高表达。 WHSC1 的敲低可减轻 LPS 诱导的 ALI 和体内细胞焦亡。此外，敲低 WHSC1 可减弱体外LPS 诱导的肺泡巨噬细胞焦亡。此外，NIMA 相关激酶 7 (NEK7) 的表达可由 WHSC1 调节，并且 NEK7 与肺泡巨噬细胞中的 NLRP3 结合。此外，WHSC1 通过调节 NEK7 介导的 NLRP3 炎性体激活来调节肺泡巨噬细胞焦亡。总之，WHSC1 在 LPS 诱导的 ALI 中高表达。 WHSC1 通过 NEK7 介导的 NLRP3 炎性体激活促进脓毒症诱导的 ALI 中肺泡巨噬细胞焦亡。 WHSC1 可能是治疗脓毒症引起的 ALI 的一个有价值的靶点。