How is IGF2BP1 involved in autophagy?
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IGF2BP1 plays a crucial role in regulating autophagy in various physiological and pathological conditions. Studies have shown that IGF2BP1 binds to transcripts encoding autophagy-related proteins, such as MAP1LC3B, ATG3, and ATG5, directly influencing the autophagy process . In atherosclerosis, elevated IGF2BP1 levels impair autophagy in macrophages, leading to foam cell formation, a hallmark of the disease . Additionally, in hepatic stellate cells, IGFBPrP1, a related protein, induces autophagy, promoting cell activation and extracellular matrix expression . Furthermore, in non-small-cell lung cancer, IGF2BP2, a related protein, stabilizes the lncRNA MALAT1, enhancing autophagy-related gene expression and promoting cancer cell proliferation . These findings collectively highlight the diverse roles of IGF2BP1 family proteins in modulating autophagy in different cellular contexts.
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| IGF2BP1, also known as IMP1, binds to autophagy-related transcripts like ATG3 and ATG5, potentially modulating the autophagy pathway in colonic epithelial cells. | |
| IGF2BP2 promotes NSCLC proliferation by stabilizing MALAT1 through an m6A-dependent mechanism, leading to increased expression of autophagy-related (ATG)12 in NSCLC cells. | |
| IGFBPrP1 activates primary hepatic stellate cells by inducing autophagy through the PI3K/Akt/mTOR signaling pathway, promoting HSC activation and extracellular matrix expression. | |
| IGF2BP1 regulates autophagy by directly modulating MAP1LC3B, enhancing autophagy flux and tissue regeneration, particularly in gastrointestinal epithelial cells, suggesting a post-transcriptional mechanism for tissue maintenance. | |
| IGF2BP1 silencing promotes autophagy by reducing RUNX1 expression, restraining ox-LDL-induced lipid accumulation and inflammation in macrophages, suggesting a potential therapeutic target in atherosclerosis. |
Related Questions
How does igf2bp2 regulate the macrophage metabolism?10 answersIGF2BP2 plays a pivotal role in regulating macrophage metabolism through various mechanisms, influencing both the phenotypic polarization and metabolic traits of macrophages. It has been observed that deletion of IGF2BP2 in macrophages enhances the M1 phenotype, which is proinflammatory, and promotes the development of dextran sulfate sodium-induced colitis. Conversely, IGF2BP2 deficiency makes macrophages refractory to IL-4 induced activation, which is crucial for the prohealing M2 phenotype, thereby alleviating pulmonary allergic inflammation. This indicates that IGF2BP2 is essential for the switch from M1 to M2 macrophage activation, targeting tuberous sclerosis 1 in an N6-methyladenosine (m6A)-dependent manner.
The regulation of IGF2BP2 expression itself is subject to complex controls and varies between species. In human and murine systems, the expression of IGF2BP2 in anti-inflammatory macrophages is synchronous, but its regulation in inflammatory macrophages differs. This suggests a nuanced role of IGF2BP2 in macrophage activation that may depend on the specific inflammatory context and species.
IGF2BP2 also modulates macrophage cellular dynamics and functionality by regulating glucose metabolism. It exhibits dual roles in controlling inflammatory phenotypes in macrophages by regulating the activation of the IGF2 receptor (IGF2R) and IGF1R, which in turn affects mitochondrial function and oxidative phosphorylation. Furthermore, IGF2BP2's interaction with the transcript encoding ATP6V1A, a component of the vacuolar ATPase (v-ATPase), highlights its role in mediating mRNA stability, which is crucial for lysosomal function and, by extension, macrophage metabolism.
Additionally, IGF2BP2's involvement in the m6A modification of RNA transcripts, such as AGAP2-AS1, further underscores its regulatory role in macrophage metabolism. This modification affects the stability of RNA transcripts, influencing macrophage polarization and the activation of signaling pathways like PI3K/AKT, which are vital for macrophage function.
In summary, IGF2BP2 regulates macrophage metabolism through a multifaceted approach that includes influencing macrophage polarization, glucose metabolism, mitochondrial function, and RNA transcript stability, thereby playing a critical role in the immune response and inflammation.
How does igf2bp3 regulate macrophage metabolism?4 answersIGF2BP3 plays a pivotal role in regulating macrophage metabolism through various mechanisms, impacting both macrophage activation and the broader inflammatory response. IGF2BP3's influence on macrophage metabolism is multifaceted, involving the modulation of macrophage polarization, mRNA stability, and signaling pathways that collectively contribute to the inflammatory and regenerative processes.
Firstly, IGF2BP3 is involved in the phenotypic polarization of macrophages, a process critical for their function in inflammation and tissue repair. It has been observed that IGF2BP3 deletion in macrophages enhances the M1 phenotype, which is proinflammatory, while also affecting the M2 phenotype, which is associated with healing and tissue repair. This indicates that IGF2BP3 plays a crucial role in balancing the proinflammatory and prohealing states of macrophages, which is essential for the resolution of inflammation and promotion of tissue repair.
Moreover, IGF2BP3's role extends to the regulation of mRNA stability and translation, impacting the expression of critical regulators of cell division and metabolism. This regulation is crucial for the proper functioning of macrophages and their response to inflammatory stimuli. The stabilization of AGAP2-AS1 by IGF2BP3 through m6A modification, for instance, promotes the expression of THBS2, which in turn activates the PI3K/AKT signaling pathway, leading to M2 polarization of macrophages. This pathway is vital for the resolution of inflammation and the promotion of tissue repair.
Additionally, IGF2BP3's regulation of macrophage metabolism is also evident in its role in myocardial infarction, where it promotes cardiomyocyte proliferation and regeneration. This indicates a broader impact of IGF2BP3 on tissue regeneration and repair mechanisms, further highlighting its importance in macrophage metabolism and function.
In summary, IGF2BP3 regulates macrophage metabolism through its involvement in macrophage polarization, mRNA stability, and activation of signaling pathways, playing a critical role in the inflammatory response and tissue repair processes.
What is the role of igf2bp2 for macrophage?4 answersThe role of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in macrophage function is multifaceted, influencing both macrophage activation and polarization, which are critical in various physiological and pathological processes. IGF2BP2 expression is differentially regulated in human and murine macrophages upon exposure to inflammatory stimuli, such as bacterial lipopolysaccharide (LPS), indicating a species-specific regulatory mechanism that affects macrophage polarization differently between humans and mice. This differential expression of IGF2BP2 is significant given its role in macrophage activation and the subsequent impact on inflammatory diseases.
IGF2BP2's involvement in macrophage polarization is particularly notable in the context of atherosclerosis (AS), where it has been shown to influence foam cell formation, a key event in AS progression. The upregulation of IGF2BP2 in macrophages exposed to oxidized low-density lipoprotein (ox-LDL) suggests its role in lipid accumulation and inflammation, which are hallmarks of AS. Furthermore, IGF2BP2 deletion in macrophages has been observed to enhance the M1 phenotype, which is associated with proinflammatory responses, while impairing the transition to the M2 phenotype, which is involved in healing and anti-inflammatory processes. This indicates that IGF2BP2 plays a crucial role in regulating the balance between proinflammatory and prohealing macrophage activation states.
Moreover, IGF2BP2's regulatory function extends to metabolic traits of macrophages, where it modulates glucose metabolism through differential activation of the IGF2 receptor (IGF2R) by low-dose IGF2 and IGF1R by high-dose IGF2. This modulation influences macrophage inflammatory phenotypes by regulating oxidative phosphorylation and DNA methylation processes, further highlighting the complex role of IGF2BP2 in macrophage functionality.
In summary, IGF2BP2 is a critical regulator of macrophage activation and polarization, with implications for inflammatory diseases, atherosclerosis, and macrophage metabolic processes. Its differential expression and regulatory mechanisms underscore the importance of IGF2BP2 in macrophage biology and its potential as a therapeutic target in diseases characterized by macrophage dysfunction.
How does igf2bp2 regulate macrophage polarization?5 answersIGF2BP2 plays a crucial role in regulating macrophage polarization, a process critical for immune response modulation and inflammation resolution. Research indicates that IGF2BP2's regulation of macrophage polarization involves several mechanisms and pathways, highlighting its potential as a therapeutic target in inflammatory diseases.
In human monocyte-derived macrophages (HMDMs), IGF2BP2 mRNA expression is significantly reduced following bacterial lipopolysaccharide (LPS) treatment, although protein levels remain unchanged initially. However, prolonged LPS exposure eventually enhances both mRNA and protein levels of IGF2BP2, suggesting a time-dependent regulatory role in macrophage activation. This finding is consistent with observations in mouse bone marrow-derived macrophages (BMDMs), indicating a conserved function across species.
IGF2BP2 deletion in macrophages leads to an enhanced M1 phenotype, promoting the development of dextran sulfate sodium-induced colitis, while simultaneously being refractory to interleukin-4 (IL-4) induced M2 activation. This suggests that IGF2BP2 facilitates the switch from M1 to M2 macrophage activation, targeting tuberous sclerosis 1 in an N6-methyladenosine (m6A)-dependent manner. Furthermore, IGF2BP2 is implicated in the regulation of macrophage polarization through the PI3K/AKT signaling pathway, as demonstrated in the context of renal cell carcinoma (RCC), where it stabilizes AGAP2-AS1 expression to promote M2 polarization.
The role of IGF2BP2 in macrophage polarization is further supported by studies on related proteins and signaling pathways. For instance, IGFBP-rP1, a related protein, has been shown to inhibit M2 polarization of macrophages through the PI3K/AKT signaling pathway. Additionally, IRF2BP2, another regulator, limits inflammatory responses in macrophages and is crucial for mediating the beneficial effects of interferon beta (IFNβ) in reducing stroke injury.
In summary, IGF2BP2 regulates macrophage polarization through multiple mechanisms, including m6A-dependent mRNA stabilization and modulation of key signaling pathways like PI3K/AKT. Its role in switching macrophage activation states from proinflammatory M1 to prohealing M2 highlights its potential as a target for therapeutic intervention in inflammatory diseases.
How is irgm involved in autophagy?5 answersIRGM is involved in autophagy by regulating selective autophagy processes such as xenophagy and mitophagy. It impacts autophagy by affecting mitochondrial fusion and fission, promoting the co-assembly of ULK1 and Beclin 1, enhancing Beclin 1 interacting partners, interacting with other key proteins, and regulating lysosomal biogenesis. IRGM also negatively regulates NLRP3 inflammasome formation, which impacts inflammation and pyroptosis. Additionally, IRGM employs two parallel approaches to restrain inflammasome activation: directly interacting with NLRP3 and PYCARD/ASC to mediate their degradation, and blocking the polymerization of NLRP3 and PYCARD. Furthermore, IRGM has been found to regulate autophagy in the context of non-alcoholic fatty liver disease (NAFLD) by altering hepatic lipid metabolism through the autophagy pathway. Overall, IRGM plays a crucial role in autophagy regulation and its involvement in various diseases highlights its significance in immunity and tumorigenesis.
Is Igf2bp1 associated with urinary tract disorders?4 answersIgf2bp1 is not mentioned in any of the provided abstracts.