Suppression of lysosomal-associated protein transmembrane 5 ameliorates cardiac function and inflammatory response by inhibiting the nuclear factor-kappa B (NF-κB) pathway after myocardial infarction in mice

Abstract

Myocardial infarction (MI) as the remarkable presentation of coronary artery disease is still a reason for morbidity and mortality in worldwide.Lysosomal-associated protein transmembrane 5 (LAPTM5) is a lysosomal-related protein found in hematopoietic tissues and has been confirmed as a positive regulator of pro-inflammatory pathways in macrophages. However, the role of LAPTM5 in MI remains unknown. In this study, we found that both mRNA and protein expression levels of LAPTM5 were significantly elevated in MI mice. Suppression of LAPTM5 in myocardial tissues decreased cardiac fibrosis and improved cardiac function after MI. At the molecular level, downregulated LAPTM5 dramatically suppressed the macrophage activation and inflammatory response via inhibiting the activation of the NF-κB pathway. Collectively, suppression of LAPTM5 in myocardial tissues inhibits the pro-inflammatory response and the cardiac dysfunction caused by MI. This study indicated that LAPTM5 as a pro-inflammatory factor plays a crucial role in MI disease.

Bioinformatic analyses reveal lysosomal-associated protein transmembrane 5 as a potential therapeutic target in lipotoxicity-induced injury in diabetic kidney disease

“…LAPTM5, a multifunctional protein, has been implicated in several cellular processes, including autophagy [ 50 ], lysosomal stabilization [ 51 ], apoptosis [ 52 ], and inflammation [ 23 , 53 ]. Its role as a pro-inflammatory factor has been well-established in macrophages [ 53 ] and myocardial infarction [ 23 ]. In this study, we found that LAPTM5 positively correlated with IL-1β、IL-6, TNF-α, and IL-8 in TECs of DKD.…”

“…Despite its established roles in these contexts, the function of LAPTM5 within the framework of DKD remains largely unexplored [ 22 ]. Previous studies showed that LAPTM5 may play a role in mitigating inflammation [ 23 , 24 ], and a key factor in the pathogenesis of DKD. This finding suggests that LAPTM5 could potentially represent a novel therapeutic target or biomarker for DKD.…”

Identification of Key Genes and Pathways in the Hippocampus after Traumatic Brain Injury: Bioinformatics Analysis and Experimental Validation

“…Among the Fc receptors, Fcgr2b could serve as one marker of the pro-inflammatory phenotype of microglia after TBI [77][78][79]. There was some evidence that Laptm5 had pro-inflammatory properties in macrophages [80]. In a chronic constriction injury in rats, Laptm5 was identified as a significant upregulated neuroinflammation-related gene that influenced neuropathic pain behavior [81].…”

The role of β-catenin in cardiac diseases

“…β-catenin might play a role in regulating MI inflammation through its interaction with NF-κB. Both the Wnt/β-catenin pathway and NF-κB were activated after MI ( Song et al, 2022 ). NF-κB is a major transcription factor in the inflammatory response that can promote the expression of proinflammatory factors and enzymes.…”