TY - JOUR
T1 - Effects of retinoic acid on the development of liver fibrosis produced by carbon tetrachloride in mice
AU - Wang, Lan
AU - Potter, James J.
AU - Rennie-Tankersley, Lynda
AU - Novitskiy, Gennadiy
AU - Sipes, Jennifer
AU - Mezey, Esteban
N1 - Funding Information:
The authors thank Dr. Michael R. Torbenson from the Department of Pathology for evaluation of the liver pathology. This study was supported by HHS/NIH grants K01AA00323 and R01AA000626.
PY - 2007/1
Y1 - 2007/1
N2 - The role of retinoic acid (RA) in liver fibrogenesis was previously studied in cultured hepatic stellate cells (HSCs). RA suppresses the expression of α2(I) collagen by means of the activities of specific nuclear receptors RARα, RXRβ and their coregulators. In this study, the effects of RA in fibrogenesis were examined in carbon tetrachloride (CCl4) induced liver fibrosis in mice. Mice were treated with CCl4 or RA and CCl4, along side control groups, for 12 weeks. RA reduced the amount of histologically detectable fibrosis produced by CCl4. This was accompanied by a attenuation of the CCl4 induced increase in α2(I) collagen mRNA and a lower (2-fold versus 3-fold) increase in liver hydroxyproline. Furthermore, RA reduced the levels of 3-nitrotyrosine (3-NT) protein adducts and thiobarbituric acid (TBA) reactive substance (TBARS) in the liver, which are formed as results of oxidative stress induced by CCl4 treatment. These in vivo findings support our previous in vitro studies in cultured HSC of the inhibitory effect of RA on type I collagen expression. The data also provide evidence that RA reduces CCl4 induced oxidative stress in liver, suggesting that the anti-fibrotic role of RA is not limited to the inhibition of type I collagen expression.
AB - The role of retinoic acid (RA) in liver fibrogenesis was previously studied in cultured hepatic stellate cells (HSCs). RA suppresses the expression of α2(I) collagen by means of the activities of specific nuclear receptors RARα, RXRβ and their coregulators. In this study, the effects of RA in fibrogenesis were examined in carbon tetrachloride (CCl4) induced liver fibrosis in mice. Mice were treated with CCl4 or RA and CCl4, along side control groups, for 12 weeks. RA reduced the amount of histologically detectable fibrosis produced by CCl4. This was accompanied by a attenuation of the CCl4 induced increase in α2(I) collagen mRNA and a lower (2-fold versus 3-fold) increase in liver hydroxyproline. Furthermore, RA reduced the levels of 3-nitrotyrosine (3-NT) protein adducts and thiobarbituric acid (TBA) reactive substance (TBARS) in the liver, which are formed as results of oxidative stress induced by CCl4 treatment. These in vivo findings support our previous in vitro studies in cultured HSC of the inhibitory effect of RA on type I collagen expression. The data also provide evidence that RA reduces CCl4 induced oxidative stress in liver, suggesting that the anti-fibrotic role of RA is not limited to the inhibition of type I collagen expression.
KW - Carbon tetrachloride
KW - Collagen
KW - Liver fibrosis
KW - Oxidative stress
KW - Retinoic acid
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U2 - 10.1016/j.bbadis.2006.08.009
DO - 10.1016/j.bbadis.2006.08.009
M3 - Article
C2 - 17011172
AN - SCOPUS:33845627110
SN - 0925-4439
VL - 1772
SP - 66
EP - 71
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 1
ER -