Effects of angiotensin II receptor antagonist, Losartan on the apoptosis, proliferation and migration of the human pancreatic stellate cells.
OBJECTIVE
To investigate the effects of AT1 (Type 1 angiotensin II receptor) antagonist (Losartan) on the apoptosis, proliferation and migration of the human pancreatic stellate cells (hPSCs).


METHODS
hPSCs were isolated from pancreatic sample of patients with pancreatic carcinoma using radioimmunoassay (RIA) technique to detect the concentration of AngII in culture media and cell homogenate. Immunocytochemistry (ICC) and in situ hybridization (ISH) methods were utilized to test AT1 expression in hPSCs. Effects of Losartan on hPSCs proliferation, apoptosis and migration were investigated using BrdU incorporation, TUNEL, flow cytometry (FCM), and phase-contrast microscope separately when cells treated with Losartan. Immunofluorescence and Western blot were applied to quantify the expression of type I collagen in hPSCs.


RESULTS
There exists AT1 expression in hPSCs, while no AngII was detected in culture media and cell homogenate. Losartan induces cell apoptosis in a dose- and time-dependent manner (apparently at 10(-5) mol/L), no pro-proliferative effect was observed in the same condition. Corresponding dosage of Losartan can also alleviate the motion capability and type I collagen content of hPSCs compared with AngII treatment and non-treatment control groups.


CONCLUSIONS
These findings suggest that paracrine not autocrine functions of AngII may have effects on hPSCs, which was mediated by AT1 expressed on cells, while Losartan may exert anti-fibrotic effects by inhibiting hPSCs motion and partly by inducing apoptosis.
Liu
Wen-Bin
WB
Shanghai No. 1 People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
Wang
Xing-Peng
XP
Wu
Kai
K
Zhang
Ru-Ling
RL
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D005355:Fibrosis; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D046790:Pancreas, Exocrine / Q000166:cytology*; D050500:Pancreatitis, Chronic / Q000188:drug therapy / Q000473:pathology
D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan