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AIM's dual role in the liver: how does it simultaneously promote and suppress disease?
In current biomedical research, apoptosis inhibitory factors (AIMs) produced by macrophages are gaining increasing attention. This protein not only plays an important role in regulating immune responses and inflammation, but also plays a key role in lipid metabolism and apoptosis. The complexity of AIM makes it exhibit relatively contradictory effects in different pathological conditions, which has triggered deep thinking in the scientific community about its dual role.
Overview
AIM is a 40 kDa protein encoded by the CD5L gene. It is primarily produced by tissue-resident macrophages and is regulated by transcriptional activation of nuclear receptors (LXR/RXR) or the transcription factor MAFB. AIM belongs to the scavenger receptor cysteine-rich (SRCR) superfamily and possesses three SRCR domains. In serum, AIM binds to IgM pentamers, preventing renal excretion and maintaining high circulating concentrations. Although AIM bound to IgM is inactive, it will separate in the event of disease and play a role in promoting disease repair.
Function
AIM has multiple roles in the body. Its diverse functions include regulating lipid metabolism and apoptosis, inhibiting cholesterol synthesis, and affecting the pathogenicity of Th17 cells. Despite the diverse effects of AIM on the regulation of inflammation, its specific roles in different contexts remain unclear. Studies have shown that AIM binds to molecules such as CD36, a membrane glycoprotein involved in a variety of cellular functions, including inflammation and atherosclerosis.
AIM has been found to be increased in autoimmune diseases, raising its potential as a biomarker, but its specific mechanisms are unclear.
Manifestations in autoimmune diseases
Elevated levels of AIM make it a potential biomarker in autoimmune diseases such as muscular dystrophy, secondary progressive multiple sclerosis, rheumatoid arthritis, and osteoarthritis. For example, in patients with knee arthritis, AIM in CD14+ macrophages may enhance the survival of synovial macrophages, thereby promoting the development of arthritis. In lupus, AIM concentrations correlate with disease activity and inflammatory markers and decrease significantly after effective treatment.
Role in cardiopulmonary diseaseAIM is mainly involved in inflammation, inhibiting macrophage apoptosis and enhancing inflammatory response in cardiovascular and pulmonary diseases. Studies have shown that in atherosclerosis, AIM is highly expressed in foamy macrophages, promoting macrophage survival and inflammatory response. Mice lacking AIM exhibited better outcomes after myocardial infarction, including improved survival and reduced heart rupture.
Dual role in liver function
The effects of AIM in the liver are quite complex. On the one hand, it promotes the inflammation-related lipolysis process in lipid metabolism; on the other hand, in the liver microenvironment, it plays a protective role by counteracting the fibrotic effect of TGFβ1. In certain liver injury models, AIM was found to counteract fibrosis and affect immune cell infiltration and macrophage type transformation. Nevertheless, in HCC, elevated AIM is associated with aggressive tumor characteristics and enhanced proliferation and resistance to apoptosis.
Role in kidney function
AIM plays a key role in acute kidney injury (AKI). According to a 2016 study published in Nature Medicine, an increase in AIM during AKI promotes the kidney's repair process, and mice lacking AIM are poor at clearing cellular debris. In the IgA nephropathy model, recombinant AIM restored tubular IgM/IgG co-deposition, suggesting its role in renal injury.
In summary, AIM plays a dual role as a regulatory factor in various diseases: promoting the development of the disease in some cases and promoting repair and recovery function in others. Can a deeper understanding of this delicate balance provide new ideas for future treatment strategies?
