FAM46C inhibits lipopolysaccharides-induced myocardial dysfunction via downregulating cellular adhesion molecules and...

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Immunology

Background:

• Sepsis triggers a systemic inflammatory response, often leading to sepsis-induced myocardial dysfunction (SIMD).
• Cellular adhesion molecules are implicated in the pathogenesis of SIMD, a critical factor in sepsis mortality.
• The role of FAM46C in SIMD remains largely unexplored.

Purpose of the Study:

• To investigate the function of FAM46C in AC16 cells and C57 mice models of sepsis.
• To elucidate the molecular mechanisms by which FAM46C influences sepsis-induced myocardial dysfunction.

Main Methods:

• Gene and protein expression analysis using real-time PCR and Western blot.
• Assessment of cell proliferation and apoptosis in response to lipopolysaccharides (LPS).
• In vivo studies involving LPS administration and TLR4 inhibition (TAK-242).

Main Results:

• A negative correlation was observed between Toll-like receptor 4 (TLR4) and FAM46C expression in sepsis.
• Overexpression of FAM46C significantly reduced LPS-induced apoptosis in AC16 cells.
• FAM46C inhibited apoptosis by downregulating cellular adhesion molecules via the p38 and ERK/MAPK signaling pathways.
• FAM46C overexpression and TLR4 inhibition attenuated LPS-induced myocardial apoptosis in vivo.

Conclusions:

• FAM46C plays a protective role in sepsis-induced myocardial dysfunction.
• FAM46C mitigates LPS-induced myocardial dysfunction by inhibiting apoptosis and downregulating cellular adhesion molecules.
• This study provides the first evidence for FAM46C's involvement in SIMD.