PMID- 19087721
OWN - NLM
STAT- MEDLINE
DCOM- 20090520
LR  - 20131121
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 88
IP  - 34
DP  - 2008 Sep 9
TI  - [Role of Rho-Rock pathways induced by angiotensin II in hepatic stellate cell 
      contraction].
PG  - 2422-6
AB  - OBJECTIVE: To investigate the mechanism of Ca(2+)-independent pathways mediated 
      by Rho-kinase in contraction of hepatic stellate cells (HSCs) induced by 
      angiotonin II (Ang II). METHODS: Human HSCs of the line HSC-T6 were cultured and 
      randomly divided into 6 groups: negative control group, Ang II group treated by 
      Ang II10 micromol/L for 15 min, Ang II + irbesartan (Ang II receptor inhibitor) 
      group, exposed to irbesartan for 60 min prior to Ang II treatment, Ang II + 
      Y27632 (Rho kinase specific inhibitor) exposed to Y27632 for 60 min prior to Ang 
      II treatment, Ang II + ML-7 (myosin light chain kinase specific inhibitor) + 
      saturo (protein kinase C specific inhibitor) group exposed to stauro for 60 min 
      prior to Ang II treatment, and Ang II + Y27632 + ML-7 + stauro group, exposed to 
      Y27632 and stauro for 60 min prior to Ang II treatment. The cell contraction was 
      detected by silicone-rubber-membrane cultivation directly. The protein levels of 
      MLC and phosphorylated MLC were detected by Western blotting 5, 15, 30, 60, and 
      120 min after Ang II treatment. RT-PCR was used to detect the expression of 
      Rock2, RhoAGTP, and RhoGEF in Ca(2+)-independent pathways mediated by Rho-kinase. 
      RESULTS: The silicone-rubber-membrane covered by Ang II treated HSCs showed 
      obvious wrinkles indicating the contraction of HSCs. The ratios of phosphorylated 
      MLC protein at the time pints 5, 15, 30, 60, and 120 min of the Ang II group to 
      the control group (0 min) were 11.7 +/- 0.1, 26.9 +/- 0.1, 11.2 +/- 0.1, 4.1 +/- 
      0.1, and 1.0 +/- 0.1, showing that Ang II increased the phosphorylated MLC 
      protein level time-dependently with the peak level at the time point of 15 
      minutes. The levels of phosphorylated MLC protein of the Ang II + irbesartan and 
      Ang II + Y27632 groups were (1.12 +/- 0.09)and (1.22 +/- 0.10) respectively, both 
      significantly lower than that of the Ang II group (1.33 +/- 0.06, both P < 0.01). 
      The level of phosphorylated MLC protein of the Ang I + ML-7 + stauro group was 
      (1.43 +/- 0.09), significantly higher than that of the Ang II + Y27632 group 
      (0.64 +/- 0.04, P < 0. 01). The level of phosphorylated MLC protein of the Ang II 
      + Y27632 + ML-7 + stauro group was (0.64 +/- 0.04), significantly lower than that 
      of the Ang II group (P = 0. 003). The mRNA expression levels of Rock2, RhoAGTP, 
      and RhoGEF of the Ang II group were (0.36 +/- 0.01), (0.80 +/- 0.01), and(0.65 
      +/- 0.11)respectively, all significantly higher than those of the control group 
      [(0.12 +/- 0.01), (0.40 +/- 0.02), and (0.33 +/- 0.09) respectively, all P = 0. 
      000], and the mRNA expression levels of Rock2, RhoAGTP, and RhoGEF of the Ang II 
      + irbesartan + group were (0.21 +/- 0.02), (0.62 +/- 0.02), and (0.41 +/- 0.10) 
      respectively, all significantly lower than those of the control group. The mRNA 
      expression levels of Rock2 (0.15 +/- 0.01) and RhoGEF (0.28 +/- 0.08) were lower, 
      but The mRNA expression level of RhoAGTP (1.14 +/- 0.02) was higher in the Ang II 
      + Y27632 group. The mRNA expression levels of Rock2, RhoAGTP, and RhoGEF of the 
      Ang II + ML-7 + stauro group were (0.22 +/- 0.01), (0.55 +/- 0.03), and (0.44 +/- 
      0.10) respectively, all significantly higher than those of the control group. The 
      mRNA expression levels of Rock2, RhoAGTP, and RhoGEF of the Ang II + Y27632 + 
      ML-7 + stauro group were (0.23 +/- 0.01), (0.83 +/- 0.02), and (0.69 +/- 0.08) 
      respectively, all significantly higher than those of the Ang II + ML-7 + stauro 
      group. CONCLUSION: Ang II induces HSCs contraction in Ca(2+)-independent pathways 
      mediated by Rho-kinase.
FAU - Zhang, Xiao-Lan
AU  - Zhang XL
AD  - Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China.
FAU - Xiao, Bing
AU  - Xiao B
FAU - Li, Xu
AU  - Li X
FAU - Huang, Mao-Liang
AU  - Huang ML
FAU - Meng, Ying
AU  - Meng Y
FAU - Li, Ying-Fei
AU  - Li YF
FAU - Wang, Yuan-Yuan
AU  - Wang YY
FAU - Song, Wei-Bing
AU  - Song WB
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Rho Guanine Nucleotide Exchange Factors)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Angiotensin II/*pharmacology
MH  - Cells, Cultured
MH  - Guanine Nucleotide Exchange Factors/metabolism
MH  - Hepatic Stellate Cells/*drug effects/*physiology
MH  - Humans
MH  - Renin-Angiotensin System
MH  - Rho Guanine Nucleotide Exchange Factors
MH  - Signal Transduction
MH  - rho-Associated Kinases/metabolism
EDAT- 2008/12/18 09:00
MHDA- 2009/05/21 09:00
CRDT- 2008/12/18 09:00
PHST- 2008/12/18 09:00 [entrez]
PHST- 2008/12/18 09:00 [pubmed]
PHST- 2009/05/21 09:00 [medline]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2008 Sep 9;88(34):2422-6.