Qian Wang1, Xin Zhang2, Shuanghong Lei3, Yi Wang4, Yongjing Zhuang5, Yi Chen5, Chao Zeng6, Huan Zhang7, Chaoxu Liu8, Gang Wang9. 1. Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China. 2. Department of Medical Psychology, Fourth Military Medical University, Xi'an, 710038, China. 3. Anorectal Department, The First People's Hospital of Longnan, Longnan, 742500, China. 4. Laboratory Animal Center, Fourth Military Medical University, Xi'an, 710038, China. 5. Department of General Surgery, No. 421 Hospital of PLA, Guangzhou, 510318, China. 6. Department of Cardiology, No. 421 Hospital of PLA, Guangzhou, 510318, China. 7. Department of Health Service, No. 421 Hospital of PLA, Guangzhou, 510318, China. 8. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 201907, China. Electronic address: chaoxuliu@yahoo.com. 9. Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China; Department of General Surgery, No. 421 Hospital of PLA, Guangzhou, 510318, China. Electronic address: wg7995@126.com.
Abstract
BACKGROUND: The morbidity and mortality associated with acute pancreatitis (AP) are largely attributable to abnormalities that occur in distant organs, such as liver and lungs. Pancreatitis-associated liver injury (PALI) remains a serious and even fatal complication during the progression of AP. However, the exact pathophysiological mechanism is still unclear. METHODS: In the present study, we used, for the first time, RNA-seq method to reveal pathways and candidate genes associated with PALI in rats. AP was induced by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. The RNA-seq results of selected genes were validated by RT-PCR and immunohistochemistry assay. RESULTS: GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis indicated that Toll like receptor 4 (TLR4) signaling pathway and transforming growth factor β1 (TGF-β1) and p38 mitogen-activated protein kinase (MAPK) signaling pathway (TGF-β1-p38 MAPK) were involved in the course of PALI. In addition, other factors were also found to be involved in the course of PALI, such as the decreased antioxidant activity, excessive production of inflammatory mediators and alterations in liver metabolism. CONCLUSIONS: The study sheds some new insight on our understanding of the pathophysiology of PALI and provides some clues to the identification of potential therapeutic targets.
BACKGROUND: The morbidity and mortality associated with acute pancreatitis (AP) are largely attributable to abnormalities that occur in distant organs, such as liver and lungs. Pancreatitis-associated liver injury (PALI) remains a serious and even fatal complication during the progression of AP. However, the exact pathophysiological mechanism is still unclear. METHODS: In the present study, we used, for the first time, RNA-seq method to reveal pathways and candidate genes associated with PALI in rats. AP was induced by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. The RNA-seq results of selected genes were validated by RT-PCR and immunohistochemistry assay. RESULTS: GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis indicated that Toll like receptor 4 (TLR4) signaling pathway and transforming growth factor β1 (TGF-β1) and p38 mitogen-activated protein kinase (MAPK) signaling pathway (TGF-β1-p38 MAPK) were involved in the course of PALI. In addition, other factors were also found to be involved in the course of PALI, such as the decreased antioxidant activity, excessive production of inflammatory mediators and alterations in liver metabolism. CONCLUSIONS: The study sheds some new insight on our understanding of the pathophysiology of PALI and provides some clues to the identification of potential therapeutic targets.