RUVBL1 bound
F-actin in cell protrusions, and increased concentration of G-actin and additional formation of actin filaments in cell protrusions. Conclusion: RUVBL1 contributes to the formation of membrane protrusions by promoting peripheral actin polymerization. These RUVBL1-actin interactions enhance the invasive properties of PDAC cells. Inhibition of binding between RUVBL1 and actin filaments may be a rational approach learn more to a targeted molecular therapy for PDAC because any such therapy would inhibit the formation of cell protrusions and consequently limit the motility and invasiveness of PDAC cells. Key Word(s): 1. pancreatic ductal adenocarcinoma; 2. AAA + ATPase; 3. invasiveness; 4. cell protrusion; 5. actin polymerization Presenting Author: MASAHIKO UCHIDA
Additional Authors: TAICHI NAKAMURA, TETSUHIDE ITO, MASAYUKI NAKAYAMA, HIROYUKI SAKATA, RYUICHI IWAKIRI, KAZUMA FUJIMOTO Corresponding Author: MASAHIKO UCHIDA Affiliations: Kyushu University, Kyushu Lumacaftor datasheet University, Saga University, Saga University, Saga University, Saga University Objective: Chronic pancreatitis (CP) worsens with drinking, and pancreatic stellate cells (PSCs) play an important role in the pathogenesis of alcoholic CP. Fractalkine is chemokines, and membrane type and soluble type is present. A membrane-bound extracellular region is cut by sheddase, and soluble type fractalkine shows migration activity for the inflammatory cell with CX3CR1 (fractalkine receptor). Serum levels of fractalkine (CX3CL1) are elevated in patients with alcoholic CP, however the mechanism remains unclear. This study aims to determine the effects of cytokines, pathogen-associated molecular patterns (PAMPs), and ethanol and its metabolites on CX3CL1 secretion by PSCs. Methods: Male Wistar/Bonn Kobori (WBN/Kob) rats were used as models PIK3C2G of CP in vivo. PSCs were isolated from 6-week-old male Wistar rats.
The effects of cytokines, PAMPs, and ethanol on chemokine production and activation of signaling pathways in PSCs in vitro were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay. Results: Expression of CX3CL1 and matrix metalloprotease (MMP)-2 was increased in the pancreas of WBN/Kob rats. The rat PSCs expressed CX3CL1, MMP-2, and a disintegrin and metalloprotease domain (ADAM) 17. Cytokines and PAMPs induced CX3CL1 release. Ethanol synergistically increased CX3CL1 release via ERK and ADAM17 activation in PSCs. Several cellular signaling cascades are activated by CX3CL1 in PSCs and associated with cell proliferation. Conclusion: We demonstrated for the first time that ethanol synergistically increased CX3CL1 release from PSCs in part through activation of ERK and ADAM17. This might be one of the mechanisms of serum CX3CL1 elevation and disease progression in patients with alcoholic CP. Key Word(s): 1. chronic pancreatitis; 2. PSCs; 3. chemokine; 4.