Aldometanib mitigates LPS-induced lung fibroblasts injury through the activation of AMPK-mediated signaling pathways

Abstract

Acute lung injury is a critical condition that severely disrupts pulmonary gas exchange, potentially causing respiratory and multiple organ failure.This condition is usually caused by various factors such as infection, which poses a serious threat to the health and life of patients and requires timely diagnosis and treatment. As a new AMPK (AMP-activated protein kinase) activator, "Aldometanib" specifically activates lysosomal AMPK by blocking the binding of aldolase to fructose-1,6-diphosphate (FBP), thereby mimicking the effects of starvation and caloric restriction. AMPK is crucial for regulating cellular metabolism and maintaining energy balance in the body. This study assessed aldometanib's impact on lung fibroblasts injury induced by Lipopolysaccharide (LPS). Therefore, we established a cell injury model of LPS-treated lung fibroblasts. The experimental results showed that aldometanib could effectively improve the proliferation inhibition of lung fibroblasts caused by LPS by evaluating cell proliferation marker molecules. Subsequent research demonstrated that aldometanib effectively mitigates inflammation and oxidative stress damage induced by LPS. We also found that aldometanib can inhibit NLRP3-mediated pyroptosis. Mechanistic study found that Aldometanib mitigates LPS-induced lung fibroblasts injury through activation of the AMPK signaling pathway. This finding introduces a novel pharmacological target for treating pulmonary inflammatory diseases and expands the potential use of AMPK activators in lung health.

Keywords: AMPK; Aldometanib; Inflammation; LPS; Lung cells.