Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis Recovery
We have previously demonstrated that the pancreas can recover from chronic pancreatitis (CP) lesions in the cerulein-induced mouse model. To explore how pancreatic recovery is achieved at the molecular level, we used RNA-sequencing (seq) and profiled transcriptomes during CP transition to recovery....
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Wiley
2021-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2021/5595464 |
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author | Yinjie Zhang Baibing Yang Joy M. Davis Madeline M. Drake Mamoun Younes Qiang Shen Zhongming Zhao Yanna Cao Tien C. Ko |
author_facet | Yinjie Zhang Baibing Yang Joy M. Davis Madeline M. Drake Mamoun Younes Qiang Shen Zhongming Zhao Yanna Cao Tien C. Ko |
author_sort | Yinjie Zhang |
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description | We have previously demonstrated that the pancreas can recover from chronic pancreatitis (CP) lesions in the cerulein-induced mouse model. To explore how pancreatic recovery is achieved at the molecular level, we used RNA-sequencing (seq) and profiled transcriptomes during CP transition to recovery. CP was induced by intraperitoneally injecting cerulein in C57BL/6 mice. Time-matched controls (CON) were given normal saline. Pancreata were harvested from mice 4 days after the final injections (designated as CP and CON) or 4 weeks after the final injections (designated as CP recovery (CPR) and control recovery (CONR)). Pancreatic RNAs were extracted for RNA-seq and quantitative (q) PCR validation. Using RNA-seq, we identified a total of 3,600 differentially expressed genes (DEGs) in CP versus CON and 166 DEGs in CPR versus CONR. There are 132 DEGs overlapped between CP and CPR and 34 DEGs unique to CPR. A number of selected pancreatic fibrosis-relevant DEGs were validated by qPCR. The top 20 gene sets enriched from DEGs shared between CP and CPR are relevant to extracellular matrix and cancer biology, whereas the top 10 gene sets enriched from DEGs specific to CPR are pertinent to DNA methylation and specific signaling pathways. In conclusion, we identified a distinct set of DEGs in association with extracellular matrix and cancer cell activities to contrast CP and CPR. Once during ongoing CP recovery, DEGs relevant to DNA methylation and specific signaling pathways were induced to express. The DEGs shared between CP and CPR and the DEGs specific to CPR may serve as the unique transcriptomic signatures and biomarkers for determining CP recovery and monitoring potential therapeutic responses at the molecular level to reflect pancreatic histological resolution. |
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institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
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series | Mediators of Inflammation |
spelling | doaj-art-df3d5abd224841549dee0f587f22d63e2025-02-03T01:24:39ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/55954645595464Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis RecoveryYinjie Zhang0Baibing Yang1Joy M. Davis2Madeline M. Drake3Mamoun Younes4Qiang Shen5Zhongming Zhao6Yanna Cao7Tien C. Ko8Department of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Pathology & Laboratory Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USACenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USAWe have previously demonstrated that the pancreas can recover from chronic pancreatitis (CP) lesions in the cerulein-induced mouse model. To explore how pancreatic recovery is achieved at the molecular level, we used RNA-sequencing (seq) and profiled transcriptomes during CP transition to recovery. CP was induced by intraperitoneally injecting cerulein in C57BL/6 mice. Time-matched controls (CON) were given normal saline. Pancreata were harvested from mice 4 days after the final injections (designated as CP and CON) or 4 weeks after the final injections (designated as CP recovery (CPR) and control recovery (CONR)). Pancreatic RNAs were extracted for RNA-seq and quantitative (q) PCR validation. Using RNA-seq, we identified a total of 3,600 differentially expressed genes (DEGs) in CP versus CON and 166 DEGs in CPR versus CONR. There are 132 DEGs overlapped between CP and CPR and 34 DEGs unique to CPR. A number of selected pancreatic fibrosis-relevant DEGs were validated by qPCR. The top 20 gene sets enriched from DEGs shared between CP and CPR are relevant to extracellular matrix and cancer biology, whereas the top 10 gene sets enriched from DEGs specific to CPR are pertinent to DNA methylation and specific signaling pathways. In conclusion, we identified a distinct set of DEGs in association with extracellular matrix and cancer cell activities to contrast CP and CPR. Once during ongoing CP recovery, DEGs relevant to DNA methylation and specific signaling pathways were induced to express. The DEGs shared between CP and CPR and the DEGs specific to CPR may serve as the unique transcriptomic signatures and biomarkers for determining CP recovery and monitoring potential therapeutic responses at the molecular level to reflect pancreatic histological resolution.http://dx.doi.org/10.1155/2021/5595464 |
spellingShingle | Yinjie Zhang Baibing Yang Joy M. Davis Madeline M. Drake Mamoun Younes Qiang Shen Zhongming Zhao Yanna Cao Tien C. Ko Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis Recovery Mediators of Inflammation |
title | Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis Recovery |
title_full | Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis Recovery |
title_fullStr | Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis Recovery |
title_full_unstemmed | Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis Recovery |
title_short | Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis Recovery |
title_sort | distinct murine pancreatic transcriptomic signatures during chronic pancreatitis recovery |
url | http://dx.doi.org/10.1155/2021/5595464 |
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