Pancreatic gene expression during recovery after pancreatitis reveals unique transcriptome profiles

Histological resolution of the murine pancreas occurs within one week after injury. Whether histological resolution constitutes pancreatic recovery at a molecular level is not known. We performed RNA-sequencing on the recovering pancreas to determine the transcriptomic profile within the histologically recovered pancreas. We show that although there is histological resolution one week after injury in mice, compared to baseline (non-injured pancreas), there are still numerous differentially expressed genes (DEGs) at one and even two weeks after injury. Overall, the findings suggest the actual recovery takes longer than initially thought given the differential transcriptomic profile in the pancreas two weeks after injury compared to the baseline pancreas. There is also the possibility of a novel emerging pancreatic transcriptome upon recovery. Acute pancreatitis was induced by caerulein hyperstimulation in both male and female C57BL/6 mice. Total RNA was extracted from the head of the murine pancreas in mice at baseline (non-injured; n=8), day 7 (post-injury; n=8), and day 14 (post-injury; n=7). Total stranded RNA libraries (ribo-depleted) were generated and sequenced on the Illumina NextSeq 500 NGS platform. RNA-seq data was analyzed for differentially expressed genes between baseline and day 7 and between baseline and day 14.

小鼠胰腺损伤后一周内即可完成组织学复原。目前尚不明确该组织学复原是否代表胰腺在分子层面已实现完全恢复。本研究对损伤后修复中的胰腺开展RNA测序（RNA-sequencing），以明确完成组织学复原的胰腺的转录组特征。研究结果显示，尽管小鼠在损伤后一周即可实现组织学复原，但与基线组（未损伤胰腺）相比，损伤后1周甚至2周的胰腺中仍存在大量差异表达基因（differentially expressed genes, DEGs）。综合而言，结合损伤后2周胰腺与基线胰腺间的转录组差异，本研究结果提示实际的胰腺恢复过程较此前根据组织学复原时间所推测的更长；此外，胰腺修复完成后，其转录组或存在全新的特征谱。本研究通过雨蛙素（caerulein）过度刺激法，在雄性和雌性C57BL/6小鼠中构建急性胰腺炎模型。分别在基线状态（未损伤，n=8）、损伤后第7天（n=8）以及损伤后第14天（n=7），从小鼠胰腺头部提取总RNA。构建链特异性总RNA文库（去除核糖体RNA），并在Illumina NextSeq 500二代测序（next-generation sequencing, NGS）平台上完成测序。对RNA测序数据进行分析，以筛选基线与损伤后第7天、基线与损伤后第14天两组间的差异表达基因。