Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Am J Pathol. 2012 Aug;181(2):499-507. doi: 10.1016/j.ajpath.2012.04.024. Epub 2012 Jun 8.
Pancreatic disease has onset in utero in humans with cystic fibrosis (CF), and progresses over time to complete destruction of the organ. The exact mechanisms leading to pancreatic damage in CF are incompletely understood. Inflammatory cells are present in the pancreas of newborn pigs with CF (CF pigs) and humans, which suggests that inflammation may have a role in the destructive process. We wondered whether tissue inflammation and genes associated with inflammatory pathways were increased in the pancreas of fetal CF pigs [83 to 90 days gestation (normal pig gestation is ~114 days)] and newborn pigs. Compared with fetal pigs without CF (non-CF pigs), in fetal CF pigs, the pancreas exhibited patchy inflammation and acinar atrophy, with progression in distribution and severity in neonatal CF pigs. Large-scale transcript profiling revealed that the pancreas in fetal and newborn CF pigs exhibited significantly increased expression of proinflammatory, complement cascade, and profibrotic genes when compared with fetal and newborn non-CF pigs. Acinar cells exhibited increased apoptosis in the pancreas of fetal and newborn CF pigs. α-Smooth muscle actin and transforming growth factor β1 were increased in both fetal and newborn CF pig pancreas, suggesting activation of profibrotic pathways. Cell proliferation and mucous cell metaplasia were detected in newborn, but not fetal, CF pigs, indicating that they were not an initiator of pathogenesis but a response. Proinflammatory, complement cascade, proapoptotic, and profibrotic pathways are activated in CF pig pancreas, and likely contribute to the destructive process.
囊性纤维化（CF）患者的胰腺疾病始于胎儿期，并随着时间的推移进展为胰腺的完全破坏。导致 CF 患者胰腺损伤的确切机制尚未完全阐明。在 CF 新生仔猪和人类的胰腺中存在炎症细胞，这表明炎症可能在破坏性过程中起作用。我们想知道在 CF 胎儿猪（妊娠 83 至 90 天[正常猪妊娠约 114 天]）和新生猪的胰腺中，组织炎症和与炎症途径相关的基因是否增加。与无 CF 的胎儿猪（非 CF 猪）相比，在 CF 胎儿猪中，胰腺表现出斑片状炎症和腺泡萎缩，在新生 CF 猪中分布和严重程度均有所进展。大规模转录谱分析显示，与胎儿和新生非 CF 猪相比，CF 胎儿和新生猪的胰腺中促炎、补体级联和促纤维化基因的表达显著增加。在 CF 胎儿和新生猪的胰腺中，腺泡细胞的凋亡增加。α-平滑肌肌动蛋白和转化生长因子β1在 CF 猪的胰腺中均增加，表明促纤维化途径被激活。在新生 CF 猪中但不在胎儿 CF 猪中检测到细胞增殖和粘蛋白细胞化生，表明它们不是发病机制的启动子，而是一种反应。在 CF 猪的胰腺中，促炎、补体级联、促凋亡和促纤维化途径被激活，可能有助于破坏性过程。
