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Identification of Grb2 protein as a potential mediator of macrophage activation in acute pancreatitis based on
Qinhao Shen1, Shuai Wang2, Keyan Wu1
1Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Introduction:
Macrophage activation is closely associated with Acute pancreatitis (AP). We screened and found that Growth factor receptor bound protein 2 (Grb2) is highly expressed in macrophages during AP. However, the relationship between Grb2 and AP is still poorly understood. In this study, we explored the role of Grb2 in AP.
Methods:
We screened for gene affecting macrophage activation in AP by combining transcriptomics with Single-cell RNA-sequence analysis. Next, the expression of Grb2 in M1/M2 macrophage activation was detected by Single-cell RNA-sequence analysis and western blot. Furthermore, the effect of Grb2 on M1/M2 macrophage activation was detected by flow cytometry. The severity of AP was assessed by histological analysis, serum amylase, serum lipase and serum inflammatory factors in vivo. NOD-like receptor thermal protein domain associated protein 3 (Nlrp3) and Nuclear factor kappa-B (NF-kB) signaling pathways were also evaluated.
Results:
Grb2 is mainly expressed in macrophages of pancreas in AP and up-regulated in M1 macrophage activation. Inhibiting Grb2 could alleviate AP by preventing M1 macrophage activation through down-regulating Nlrp3 and NF-κB.
Discussion:
Inhibition of Grb2 can effectively prevent M1 macrophage activation and alleviate AP. Grb2 may potentially be an effective target of macrophage activation for the treatment of AP.
Insights
Growth factor receptor bound protein 2 (Grb2) is highly expressed in macrophages during acute pancreatitis (AP). Inhibiting Grb2 alleviates AP by preventing M1 macrophage activation, suggesting Grb2 as a potential therapeutic target.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Macrophage activation is a key factor in acute pancreatitis (AP).
- Growth factor receptor bound protein 2 (Grb2) is upregulated in pancreatic macrophages during AP.
- The specific role of Grb2 in AP pathogenesis remains unclear.
Purpose of the Study:
- To investigate the role of Grb2 in macrophage activation during AP.
- To explore the therapeutic potential of targeting Grb2 in AP.
Main Methods:
- Transcriptomics and single-cell RNA sequencing identified Grb2 in AP macrophages.
- Flow cytometry and western blot assessed Grb2's effect on M1/M2 macrophage activation.
- In vivo studies evaluated AP severity and Nlrp3/NF-κB pathways after Grb2 inhibition.
Main Results:
- Grb2 is primarily expressed in pancreatic macrophages in AP and upregulated in M1 macrophages.
- Inhibiting Grb2 reduced M1 macrophage activation.
- Grb2 inhibition alleviated AP severity by downregulating Nlrp3 and NF-κB signaling.
Conclusions:
- Grb2 inhibition effectively prevents M1 macrophage activation and ameliorates AP.
- Grb2 represents a promising therapeutic target for modulating macrophage activation in AP treatment.
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