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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Main Authors: Yinjie Zhang, Baibing Yang, Joy M. Davis, Madeline M. Drake, Mamoun Younes, Qiang Shen, Zhongming Zhao, Yanna Cao, Tien C. Ko
Format: Article
Language:English
Published: Wiley 2021-01-01
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
collection DOAJ
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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publishDate 2021-01-01
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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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