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Dissertation zugänglich unter
URN: urn:nbn:de:gbv:18-58762
URL: http://ediss.sub.uni-hamburg.de/volltexte/2012/5876/


CCK1- und CCK2- Rezeptoren werden auf pankreatischen Sternzellen exprimiert und induzieren die Kollagensynthese

Seiz, Oliver Walter

Originalveröffentlichung: (2011) J Biol Chem. 2010 Dec 10;285(50):38905-14
pdf-Format:
 Dokument 1.pdf (4.476 KB) 


Freie Schlagwörter (Deutsch): Sternzelle , Cholecystokinin , Gastrin , Kollagensynthese
Freie Schlagwörter (Englisch): stellatecells , pancreas , cholecystokinine , collagensynthesis
Basisklassifikation: 44.87 , 44.61
Institut: Medizin
DDC-Sachgruppe: Medizin, Gesundheit
Dokumentart: Dissertation
Hauptberichter: Bläker, Michael (PD Dr.)
Sprache: Deutsch
Tag der mündlichen Prüfung: 25.09.2012
Erstellungsjahr: 2011
Publikationsdatum: 25.10.2012
Kurzfassung auf Englisch: 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 to TGF-beta- 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 inhibitors, we found that Akt activation is mainly mediated by CCK2R. Akt activation by CCK and gastrin could be inhibited by PI3K inhibitor wortmannin. Activation of ERK and downstream target Elk-1 could be inhibited by MEK-inhibitor U0126.
These data suggest that CCK and gastrin have a direct activating effect 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-beta both CCK and gastrin inhibit proliferation in PSC.

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