Deletion of CD177 exacerbates acute pancreatitis-associated lung injury and colonic barrier dysfunction in a mouse model of acute pancreatitis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE260762 | GEO | 2026/03/04
REPOSITORIES: GEO
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Project description:Acute pancreatitis (AP) is a common and severe inflammatory disease of the abdomen. Recent studies have shown that macrophages play a crucial role in AP. 4-octyl itaconate (4OI), a derivative of the cell metabolism intermediate itaconate (ITA), has demonstrated significant anti-inflammatory effects in various cell and disease models. In this study, we investigated the potential role and mechanism of 4OI in both in vivo and in vitro models of AP.After administering 25 mg/kg of 4OI to mice and inducing AP with caerulein or L-Arg, we found that 4OI significantly alleviated the severity of AP: serum amylase and lipase levels were significantly reduced, histopathological scores decreased, and levels of inflammatory factors were notably lower. Additionally, macrophage infiltration and M1 polarization were significantly reduced. Through in vitro experiments, we further explored the molecular mechanism by which 4OI inhibits the inflammatory response in macrophages. We discovered that 4OI reduces macrophage polarization to the pro-inflammatory M1 type and decreases the expression of inflammation-related genes. We also found that 4OI exerts its anti-inflammatory effects by promoting the Nrf2 signaling pathway and inhibiting the Sting signaling pathway. In conclusion, this study reveals the anti-inflammatory effects of 4OI in AP and its potential clinical therapeutic value.
2024-09-18 | GSE277097 | GEO
Project description:The presence of acute pancreatitis-induced pancreatic necrosis and systemic inflammation is closely related to the prognosis and severity of the disease. Pentraxin 3 is a mediator that aggravates cell injury, and its activation is closely related to oxidative stress and reactive oxygen species generation. This study aims to explore whether PTX3 regulates AP pancreatic necrosis and reveal its potential mechanism of action. By using AP time gradient transcriptomics, proteomics, and liquid chip combined analysis methods, we screened and found a close association between PTX3 and AP. Subsequently, we constructed a classical cerulein-induced in vivo AP model and utilized a CCK-induced in vitro acinar cell injury model to determine the expression of PTX3 and its regulatory role on AP. The results showed that PTX3 presented a high expression level in the cerulein-induced AP model; while after the intervention of recombinant protein PTX3, more severe pancreatic tissue damage and increased serum amylase were observed; in addition, the expression level of PTX3 was significantly higher than that of other proteins, mitochondrial membrane potential decreased and reactive oxygen species levels increased in the in vitro model and were regulated through the oxidative phosphorylation pathway. In conclusion, multi-omics integrated analysis confirmed the close association between Pentraxin 3 and AP and revealed that it exacerbates acute pancreatitis acinar cell injury by mediating oxidative phosphorylation processes.
2025-02-06 | PXD060567 |
Project description:To elucidate the role of macrophage Anxa1 in the pathogenesis of AP, we intercrossed Anxa1flox/flox (Anxa1f/f or Anxa1 WT, as control) with Lyz2-Cre mice to create myeloid-specific Anxa1-knockout (Anxa1CKO) mice. We induced AP with repeated injection of cerulein in Anxa1CKO and Anxa1f/f littermates and examined the pancreas injury and inflammation. Pancreas tissue samples were collected at 12 hours after the first cerulein injection and performed RNA-seq.
2023-12-15 | GSE249714 | GEO
Project description:Background: The therapeutic and protective efects of human umbilical cord mesenchymal stem cells-exosomes (hucMSC-Exs) on traumatic pancreatitis (TP) remain unknown. Here, we established a rat model of TP and evaluated and compared the therapeutic efects of hucMSC-Exs. Methods: HucMSC-Exs were obtained by ultracentrifugation and identifed using transmission electron microscopy and western blot analysis. TP rats were treated by tail vein injection of hUC-MSCs and hucMSC-Exs. Their homing in rats was observed by performing fuorescence microscopy. Rat pancreatic tissue was subjected to high-throughput sequence to determine transcriptome expression levels. The degree of pancreatic tissue damage was assessed by HE staining, the expression levels of amylase, lipase, and infammatory cytokines were detected by ELISA, apoptosis was detected by TUNEL assay, and the expression levels of various apoptosis-related proteins were detected by western-blot. The expression levels of apoptosis-related molecular markers were detected by RT-qPCR. Results: The colonization of exosomes was observed in pancreatic tissue. Compared to TP group, the histopathological score of pancreas was signifcantly decreased in the TP+hucMSC-Exs group (P<0.05). Compared to TP group, the activity of serum amylase and lipase was signifcantly decreased (P<0.05). The expression levels of IL-6 and TNF-α were signifcantly decreased, while those of IL-10 and TGF-β were signifcantly increased (P<0.05). The apoptosis index of the TP group was signifcantly increased (P<0.05), whereas that of the TP+hucMSC-Exs groups was signifcantly decreased (P<0.05). Compared to TP group, the expression levels of Bax, Bcl-2, and Caspase-3 were signifcantly decreased in the TP+hUC-MSCs group and TP+hucMSC-Exs group (P<0.05). Conclusion: HucMSC-Exs can colonize injured pancreatic tissue, inhibit the apoptosis of acinar cells, and control the systemic infammatory response to facilitate the repair of pancreatic tissue.
2022-10-04 | GSE214370 | GEO
Project description:Neutrophils are the most abundant circulating leukocyte population that play critical roles in neuroinflammation after ischemic stroke. CD177, a glycoprotein on neutrophils, is emerging as an important immune regulator which fundamentally affects multiple inflammatory diseases. However, the role and regulatory mechanism of CD177 protein of neutrophils in neuroinflammation remains elusive. Using single-cell RNA sequencing (scRNA-Seq), we characterized CD177high neutrophils as a novel anti-inflammatory subset in response to ischemic stroke.
2025-03-27 | GSE293098 | GEO
Project description:Methods for differentiating human pluripotent stem cells to pancreatic and liver lineages in vitro have been limited by the inability to identify and isolate distinct endodermal subpopulations specific to these two organs. Here we report that pancreatic and hepatic progenitors can be isolated using the surface markers CD177/NB1 glycoprotein and inducible T-cell costimulatory ligand CD275/ICOSL, respectively, from seemingly homogeneous definitive endoderm derived from human pluripotent stem cells. Anterior definitive endoderm (ADE) subpopulations identified by CD177 and CD275 show inverse activation of canonical and noncanonical WNT signaling. CD177+ ADE expresses and synthesizes the secreted WNT, NODAL and BMP antagonist CERBERUS1 and is specified toward the pancreatic fate. CD275+ ADE receives canonical Wnt signaling and is specified toward the liver fate. Isolated CD177+ ADE differentiates more homogeneously into pancreatic progenitors and into more functionally mature and glucose-responsive β-like cells in vitro compared with cells from unsorted differentiation cultures.
2020-04-27 | GSE113791 | GEO
Project description:Purpose: The purpose of this study was to compare the hepatic transcriptome in the control group, acute pancreatitis, and severe acute pancreatitis, in order to identify metabolic gene changes during pancreatitis. Methods: 6-week Balb/c mice were subjected to AP (caerulein), SAP (caerulein and LPS) and control (saline), and mice liver tissues were harvested at 24 hours for RNA preparation (n=8 each group). Results: Among 11952 mapped genes, 8977 differentially expressed genes were identified by RNA-seq, including 351 genes induced in AP compare to Control and 5249 genes down regulated in SAP compare to AP. The genes up regulated were mainly related to fatty acid oxidation and ketone body synthesis especially Cpt2 and Acadvl, while genes that down regulated were associated with energy metabolism and inflammation. The overlap of two gene sets were 96 genes that involved in fatty acid metabolism. Conclusions: Our study revealed that in AP, genes associated with ketone body synthesis are upregulated in liver, in SAP, fatty acid oxidation related genes are downregulated in liver. Our data revealed the crosstalk between pancreas and liver, illustrated the difference of metabolism in AP and SAP.
2022-04-06 | GSE151927 | GEO
Project description:To investigate the transcriptional effects of CD177+ neutrophils on microglia in spinal cord injuries (SCI), we adapted a co-culture system containing isolated neutrophils from Cd177 WT or KO mice post-SCI and isolated microglia. Each group had a biological repeat (n=3).
2024-09-10 | GSE276429 | GEO
Project description:The inflammatory immune response mediated by neutrophils is closely related to the progression of acute pancreatitis. Previous studies confirmed that CD177 is a neutrophil-specific marker involved in the pathogenesis of conditions such as systemic vasculitis, asthma, and polycythemia vera. Neutrophil extracellular trap (NET) formation is a specific death program by which neutrophils release nuclear DNA covered with histones, granule proteins, etc. It also plays an important role in host defense and various pathological reactions. However, the function of CD177 in regulating the generation of NETs and the development of acute pancreatitis (AP) is unclear. In our manuscript, CD177 was significantly elevated in blood neutrophils in patients and positively correlated with the AP disease severity. Then, recombinant human CD177 protein (rhCD177) could significantly improve pancreatic injury and the inflammatory response in AP mice, and reduce AP-related lung injury. Mechanistically, we found that rhCD177 could inhibit the formation of NETs by reducing reactive oxygen species (ROS) and myeloperoxidase (MPO)/citrullinated histone H3 (CitH3) release. For the first time, we discovered the potential of rhCD177 to protect AP in mice and inhibit the NET formation of AP. CD177 may be a potential treatment strategy for preventing or inhibiting the aggravation of AP.
| S-EPMC10094768 | biostudies-literature
Project description:To investigate the transcriptional effects of CD177+ neutrophils on macrophages in spinal cord injuries (SCI), we adapted a co-culture system containing isolated neutrophils from Cd177 WT or KO mice post-SCI and bone marrow-derived macrophages (BMDMs). Each group had a biological repeat (n=3).
2024-09-10 | GSE276427 | GEO