Effect of ligand of peroxisome proliferator-activated receptor gamma on the biological characters of hepatic stellate cells.
OBJECTIVE
To study the effect of rosiglitazone, which is a ligand of peroxisome proliferator-activated receptor gamma (PPARgamma), on the expression of PPARgamma in hepatic stellate cells (HSCs) and on the biological characteristics of HSCs.


METHODS
The activated HSCs were divided into three groups: control group, 3 micromol/L rosiglitazone group, and 10 micromol/L rosiglitazone group. The expression of PPARgamma, alpha-smooth muscle actin (alpha-SMA), and type I and III collagen was detected by RT-PCR, Western blot and immunocytochemical staining, respectively. Cell proliferation was determined with methylthiazolyltetrazolium (MTT) colorimetric assay. Cell apoptosis was demonstrated with flow cytometry.


RESULTS
The expression of PPARgamma at mRNA and protein level markedly increased in HSCs of 10 micromol/L rosiglitazone group (t value was 10.870 and 4.627 respectively, P<0.01 in both). The proliferation of HSCs in 10 micromol/L rosiglitazone group decreased significantly (t = 5.542, P<0.01), alpha-SMA expression level and type I collagen synthesis ability were also reduced vs controls (t value = 10.256 and 14.627 respectively, P<0.01 in both). The apoptotic rate of HSCs significantly increased in 10 micromol/L rosiglitazone group vs control (chi(2) = 16.682, P<0.01).


CONCLUSIONS
By increasing expression of PPARgamma in activated HSCs, rosiglitazone, an agonist of PPARgamma, decreases alpha-SMA expression and type I collagen synthesis, inhibits cell proliferation, and induces cell apoptosis.
Guo
Yan-Tong
YT
Department of General Surgery, Peking University People's Hospital, Beijing, China.
Leng
Xi-Sheng
XS
Li
Tao
T
Peng
Ji-Run
JR
Song
Sheng-Han
SH
Xiong
Liang-Fa
LF
Qin
Zhi-Zhong
ZZ
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D000199:Actins; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D003094:Collagen; D004247:DNA