Expression of angiotensin II type 1 receptor in rat hepatic stellate cells and its effects on cell growth and collagen production.
OBJECTIVE
To investigate the contribution of angiotensin II towards the process of hepatic fibrosis that is largely due to hepatic stellate cell growth.


METHODS
Adult rat hepatic stellate cells were cultured and checked for the expression of angiotensin II receptor 1a (AT(1a)) mRNA by RT-PCR and sequence analysis. The effects of angiotensin II were observed on stimulation of hepatic stellate cell growth detected by MTT assays, (3)H-thymidine incorporation and cell count, and collagen synthesis by (3)H-proline incorporation.


RESULTS
We demonstrated that cultured adult rat hepatic stellate cells expressed AT(1a) mRNA, and angiotensin II in a concentration-dependent manner stimulated hepatic stellate cell growth at a concentration of 10(-7)-10(-9) mol/l and collagen synthesis at a concentration of 10(-6)-10(-10) mol/l. Also, AT(1a) receptor antagonist, in a concentration-dependent manner, blocked the cell growth from 10(-6) to 10(-8) mol/l and collagen synthesis from 10(-6) to 10(-9) mol/l.


CONCLUSIONS
The results provided direct evidence that AT(1a) mRNA was expressed in rat hepatic stellate cells and angiotensin II could contribute towards the development of hepatic fibrosis via AT(1a) receptor.
Zhang
Yijun
Y
Department of Gerontology, LiuHua Bridge Hospital, The First Military Medical University, Guangzhou, PR China.
Yang
Xishan
X
Wu
Pingsheng
P
Xu
Li
L
Liao
Guiqing
G
Yang
Guoping
G
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D003094:Collagen / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D003094:Collagen; D019808:Losartan