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.
Project description:Acute pancreatitis (AP) is an inflammatory disease with a mild to severe course, local and systemic complications, and a high mortality rate. Macrophage activation correlates with disease severity.Single cell RNA-sequencing was performed to identify inflammatory signals during AP and recovery using the blood from experimental AP model. We demonstrate that myeloid-ANXA1 expression is upregulated in peripheral blood during the initial phase of AP.
Project description:Humanized PRSS1 transgenic mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were screened by proteomics using pancreatic tissues of PRSS1 AP mice.
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.
Project description:MicroRNAs in body fluids are becoming interesting markers for disease state. Here we assessed their presence in Mesenteric Lymph to identify candidate biomarkers for pancreatitis using a rat model of the disease. We used Affymetrix microRNA arrays to assess the differences in mesenteric lymph fluid miRNAs in a taurocholate induced rat model of pancreatitis Mesenteric lymph was collected from five biological replicates from control sham operated animals (SHAM), fluid resuscitated taurocholate induced acute pancreatitis (RAP) and non-resuscitated taurocholate induced pancreatitis animals (AP). The latter group represent a more severe form of the disease.
Project description:Annexin 1 (ANXA1), an endogenous anti-inflammatory protein which modulates cellular processes such as proliferation, differentiation and apoptosis has been implicated in cancer initiation and progression. ANXA1 was previously shown to be regulated by hsa-miR-196a and promoted cell proliferation and anchorarge-dependent growth and suppressed apoptosis. However, whether ANXA1 itself regulates miRNA expression is unknown. Therefore, in this study, we investigated the regulation of miRNA by ANXA1 in breast cancer cells. Using microarray technology, 12 miRNAs were found to be significantly and consistently downregulated in MCF-7 cells (MCF-V5) overexpressing ANXA1 overexpressing MCF-7 cells (MCF-V5). Hsa-miR-26b* and hsa-miR-562 were chosen for further investigation.The data suggest that miR-26b* and miR-562 may play a role in ANXA1-induced migration and possibly angiogenesis by targeting NFKB and point towards a potential therapeutic target for breast cancer. Breast cancer MCF-7 cells (MCF-V5) overexpressing ANXA1 were cultured for RNA extraction and hybridization on Affymetrix miRNA microarrays. These were compared against the control, which were MCF-7 cells (MCF-EV) carrying an empty expression vector. Expression analyses were carried out in triplicates
Project description:Peripheral blood was collected from 87 patients with acute pancreatitis (AP) of varying severity (Mild=57, Moderately-Severe=20, Severe=10) within 24 hours of presentation to the hospital and from 32 healthy controls. RNA-Seq was performed to identify changes in expression in severe AP cf. mild, moderately-severe, and healthy controls.
Project description:Annexin 1 (ANXA1), an endogenous anti-inflammatory protein which modulates cellular processes such as proliferation, differentiation and apoptosis has been implicated in cancer initiation and progression. ANXA1 was previously shown to be regulated by hsa-miR-196a and promoted cell proliferation and anchorarge-dependent growth and suppressed apoptosis. However, whether ANXA1 itself regulates miRNA expression is unknown. Therefore, in this study, we investigated the regulation of miRNA by ANXA1 in breast cancer cells. Using microarray technology, 12 miRNAs were found to be significantly and consistently downregulated in MCF-7 cells (MCF-V5) overexpressing ANXA1 overexpressing MCF-7 cells (MCF-V5). Hsa-miR-26b* and hsa-miR-562 were chosen for further investigation.The data suggest that miR-26b* and miR-562 may play a role in ANXA1-induced migration and possibly angiogenesis by targeting NFKB and point towards a potential therapeutic target for breast cancer.