CCK1 and CCK2 receptors are expressed on pancreatic stellate cells and induce collagen production.
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CCK1 and CCK2 receptors are expressed on pancreatic stellate cells and induce collagen production. / Berna, Marc; Seiz, Oliver; Nast, Jan Friso; Benten, Daniel; Bläker, Michael; Koch, Johannes; Lohse, Ansgar W.; Pace, Andrea.
In: J BIOL CHEM, Vol. 285, No. 50, 50, 2010, p. 38905-38914.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CCK1 and CCK2 receptors are expressed on pancreatic stellate cells and induce collagen production.
AU - Berna, Marc
AU - Seiz, Oliver
AU - Nast, Jan Friso
AU - Benten, Daniel
AU - Bläker, Michael
AU - Koch, Johannes
AU - Lohse, Ansgar W.
AU - Pace, Andrea
PY - 2010
Y1 - 2010
N2 - The gastrointestinal hormone cholecystokinin (CCK) can induce acute pancreatitis in rodents through its action on acinar cells. Treatment with CCK, in combination with other agents, represents the most commonly used model to induce experimental chronic pancreatitis. Pancreatic stellate cells (PSC) are responsible for pancreatic fibrosis and therefore play a predominant role in the genesis of chronic pancreatitis. However, it is not known whether PSC express CCK receptors. Using real time PCR techniques, we demonstrate that CCK1 and CCK2 receptors are expressed on rat PSC. Interestingly both CCK and gastrin significantly induced type I collagen synthesis. Moreover, both inhibit proliferation. These effects are comparable with TGF- -stimulated PSC. Furthermore, the natural agonists CCK and gastrin induce activation of pro-fibrogenic pathways Akt, ERK, and Src. Using specific CCK1 and CCK2 receptor (CCK2R) inhibitors, we found that Akt activation is mainly mediated by CCK2R. Akt activation by CCK and gastrin could be inhibited by the PI3K inhibitor wortmannin. Activation of ERK and the downstream target Elk-1 could be inhibited by the MEK inhibitor U0126. These data suggest that CCK and gastrin have direct activating effects on PSC, are able to induce collagen synthesis in these cells, and therefore appear to be important regulators of pancreatic fibrogenesis. Furthermore, similar to TGF- , both CCK and gastrin inhibit proliferation in PSC.
AB - The gastrointestinal hormone cholecystokinin (CCK) can induce acute pancreatitis in rodents through its action on acinar cells. Treatment with CCK, in combination with other agents, represents the most commonly used model to induce experimental chronic pancreatitis. Pancreatic stellate cells (PSC) are responsible for pancreatic fibrosis and therefore play a predominant role in the genesis of chronic pancreatitis. However, it is not known whether PSC express CCK receptors. Using real time PCR techniques, we demonstrate that CCK1 and CCK2 receptors are expressed on rat PSC. Interestingly both CCK and gastrin significantly induced type I collagen synthesis. Moreover, both inhibit proliferation. These effects are comparable with TGF- -stimulated PSC. Furthermore, the natural agonists CCK and gastrin induce activation of pro-fibrogenic pathways Akt, ERK, and Src. Using specific CCK1 and CCK2 receptor (CCK2R) inhibitors, we found that Akt activation is mainly mediated by CCK2R. Akt activation by CCK and gastrin could be inhibited by the PI3K inhibitor wortmannin. Activation of ERK and the downstream target Elk-1 could be inhibited by the MEK inhibitor U0126. These data suggest that CCK and gastrin have direct activating effects on PSC, are able to induce collagen synthesis in these cells, and therefore appear to be important regulators of pancreatic fibrogenesis. Furthermore, similar to TGF- , both CCK and gastrin inhibit proliferation in PSC.
M3 - SCORING: Zeitschriftenaufsatz
VL - 285
SP - 38905
EP - 38914
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 50
M1 - 50
ER -
