title: Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate.
abstract: Trypsinogen activation is the initial factor involved in the development of all types of acute pancreatitis (AP) and has been suggested to be regulated by protein kinases. In the present study, AR42J rat pancreatic acinar cells were treated with taurolithocholic acid 3-sulfate (TLC-S), and trypsinogen activation was detected with bis-(CBZ-L-isoleucyl-L-prolyl-L-arginine amide) dihydrochloride (BZiPAR) staining and flow cytometry. Differentially expressed protein kinase genes were screened by Gene Chip analysis, and the functions of these kinases were analyzed. A significantly increased activation of trypsinogen in AR42J cells following treatment with TLC-S was observed. A total of 22 differentially expressed protein kinase genes were found in the TLC-S group, among which 19 genes were upregulated and 3 were downregulated. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, kinase genes of the same KEGG pathways were connected to create a network through signaling pathways, and 10 nodes of kinases were identified, which were mitogen-activated protein kinase (Mapk)8, Mapk14, Map2k4, interleukin-1 receptor-associated kinase 3 (Irak3), ribosomal protein S6 kinase, 90 kDa, polypeptide 2 (Rps6ka2), protein kinase C, alpha (Prkca), v-yes-1 Yamaguchi sarcoma viral related oncogene homolog (Lyn), protein tyrosine kinase 2 beta (Ptk2b), p21 protein (Cdc42/Rac)-activated kinase 4 (Pak4) and FYN oncogene related to SRC, FGR, YES (Fyn). The interactions between signaling pathways were further analyzed and a network was created. MAPK and calcium signaling pathways were found to be located at the center of the network. Thus, protein kinases constitute potential drug targets for AP treatment.
authors: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China.
authors: Biao
authors: B
authors: Ma
authors: Lin
authors: L
authors: Wu
authors: Ming
authors: M
authors: Lu
authors: Bo
authors: B
authors: Gao
authors: Xin
authors: X
authors: Qiao
authors: Bei
authors: B
authors: Sun
authors: Dongbo
authors: D
authors: Xue
authors: Weihui
authors: W
authors: Zhang
mesh_terms: D061354:Acinar Cells / Q000187:drug effects* / Q000201:enzymology*; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics; D010179:Pancreas / Q000166:cytology*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013658:Taurolithocholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D014362:Trypsinogen / Q000378:metabolism*
chemical_list: C066776:taurolithocholic acid 3-sulfate; D013658:Taurolithocholic Acid; D014362:Trypsinogen; D011494:Protein Kinases