Open AccessCARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9‐dependent NF‐κB and P38MAPKs pathway
Author(s) -
Yang Zhiwen,
Meng Xiaoxiao,
Zhang Chun,
Xu Ping
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13040
Subject(s) - gene silencing , nf κb , cancer research , nfkb1 , pancreatitis , acute pancreatitis , small interfering rna , signal transduction , microbiology and biotechnology , chemistry , medicine , gene , biology , transfection , biochemistry , transcription factor
We previously reported the up‐regulation of caspase recruitment domain 9 ( CARD9 ) expressions in severe acute pancreatitis (SAP) patients, but little is known about its regulation. In this study, small interfering RNA (siRNA) was used to reduce the levels of CARD9 expression in sodium taurocholate‐stimulated SAP rats. CARD9 was overexpressed in SAP rats, which correlated with the severity of pancreatitis. When compared to the untreated group, the cohort that received the siRNA treatment demonstrated a significant reduction in pancreatic injury, neutrophil infiltration, myeloperoxidase activity and pro‐inflammatory cytokines. Furthermore, siRNAs showed that the reduction of CARD9 in SAP rats down‐regulated the expression of NF‐κBp65 and P38MAPK which are involved in the transcription and release of a wide variety of inflammatory cytokines. These findings provide evidence that CARD9 is up‐regulated in SAP rats and acts as a potential therapeutic target for the treatment thereof. Blocking the activation of NF‐κB and P38MAPK via siRNA‐mediated gene knock‐down of CARD9 appears to reduce the inflammatory response in pancreatic tissue.