AT1A-deficient mice show less severe progression of liver fibrosis induced by CCl(4).
The renin-angiotensin system has been shown to contribute to fibrogenesis in varieties of organs, including the liver. Here, we investigated whether the angiotensin II type 1A receptor (AT1A) is implicated in the development of liver fibrosis, using AT1A-deficient and wild-type (WT) mice. After single dose of carbon tetrachloride (CCl(4)), there were no significant differences between two groups with regard to hepatic inflammation and necrosis. After 4 weeks of treatment with CCl(4), histological examination revealed that AT1A-deficient mice showed less infiltration of inflammatory cells and less severe progression of liver fibrosis compared with WT mice. These findings were accompanied by the hepatic content of hydoxyproline and the expression of alpha-smooth muscle actin (alpha SMA). The level of transforming growth factor-beta 1 (TGF-beta 1) messenger RNA was markedly higher in WT mice when compared with AT1A-deficient mice. These results confirm that signaling via AT1A plays a pivotal role in hepatic fibrogenesis.
Kanno
Keishi
K
Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
Tazuma
Susumu
S
Chayama
Kazuaki
K
D000818:Animals; D001483:Base Sequence; D002251:Carbon Tetrachloride / Q000633:toxicity*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017931:DNA Primers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride; D006909:Hydroxyproline