Lipin3 deficiency aggravates cisplatin-induced acute kidney injury by activating the Sirt1-p21-Caspase 3-GSDME pyroptosis pathway, while Lipin3 overexpression exerts a protective effect.
Does Lipin3 deficiency aggravate cisplatin-induced acute kidney injury in preclinical models?
Lipin3 deficiency exacerbates cisplatin-induced acute kidney injury by activating the Sirt1-p21-Caspase 3-GSDME pyroptosis pathway, suggesting Lipin3 is a potential therapeutic target.
. The findings indicated that (1) Lipin3 was obviously increased in AKI patients, as well as cisplatin induced mice and cells; (2) Lipin3-null mice presented with more severe AKI symptoms compared to WT mice after cisplatin treatment; (3) Lipin3 played crucial role in regulating cell death and mitochondrial function after cisplatin treatment; (4) In terms of mechanism, Lipin3 regulated these phenotypes through its interaction with Sirt1, which activated the p21-Caspase 3-GSDME pathway. Our study suggests that Lipin3 could be pivotal in pyroptosis and AKI. Decreased Lipin3 levels in the kidney may potentially contribute as a risk factor for exacerbating AKI.
Liu et al. (Mon,) conducted a other in Acute kidney injury (n=72). Lipin3 knockout / overexpression vs. Wild-type / Empty vector was evaluated on Severity of acute kidney injury (BUN, creatinine, tubular damage). Lipin3 deficiency aggravates cisplatin-induced acute kidney injury by activating the Sirt1-p21-Caspase 3-GSDME pyroptosis pathway, while Lipin3 overexpression exerts a protective effect.