Effects of retinoic acid on the development of liver fibrosis produced by carbon tetrachloride in mice

Wang, Lan; Potter, James J.; Rennie-Tankersley, Lynda; Novitskiy, Gennadiy; Sipes, Jennifer; Mezey, Esteban

doi:10.1016/j.bbadis.2006.08.009

Cited by 62 publications

(46 citation statements)

References 41 publications

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“…In an experimental model of liver fibrogenesis in mice, Wang et al (2007) observed that retinoic acid, a potent metabolite of vitamin A, suppressed the type I collagen production in liver, reducing the hepatic injury caused by oxidative stress. Retinoic acid is a potent antioxidant, and its presence is necessary to alleviate the liver injury mediated by reactive oxygen species (Tamiguchi et al, 2004).…”

Section: Discussionmentioning

confidence: 98%

Vitamin A deficiency injures liver parenchyma and alters the expression of hepatic extracellular matrix

Aguilar

Genta

Oliveros

et al. 2008

J of Applied Toxicology

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Vitamin A is an essential lipid-soluble nutrient that is crucial for morphogenesis and adult tissue maintenance. The retinoid homeostasis in the liver depends on a regular supply of vitamin A from an adequate dietary intake to preserve the normal organ structure and functions. This study focuses on the effect of vitamin A deficiency on the morphology and extracellular proteins expression of the liver in adult Wistar rats. Animals were fed with a normal (control group) or deficient vitamin A diet for 3 months. At the end of the experimental period, histological examination of the livers under light and electron microscopy revealed that vitamin A deficiency produced a loss of hepatocyte cord disposition with an irregular parenchymal organization. Abundant fat droplets were present in the cytoplasm of the hepatocytes. Elongated myofibroblastic-like cells with an irregular cytoplasmic process and without lipid droplets could be seen at the perisinusoidal space, where an elevated intensity of alpha smooth muscle actin (alpha-SMA) was observed. These results suggest that an activation of hepatic stellate cells (HSCs) occurred. Moreover, immunochemical methods revealed that vitamin A deficiency led to an increased expression of hepatic fibronectin, laminin and collagen type IV. We propose that vitamin A deprivation caused liver injury and that HSCs underwent a process of activation in which they produced alpha-SMA and synthesized extracellular components. These changes may be a factor predisposing to liver fibrosis. In consequence, vitamin A deprivation could affect human and animal health.

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Section: Discussionmentioning

confidence: 98%

Vitamin A deficiency injures liver parenchyma and alters the expression of hepatic extracellular matrix

Aguilar

Genta

Oliveros

et al. 2008

J of Applied Toxicology

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“…To quantify fibronectin immunostaining, the integrated image intensity in eight consecutively selected nonoverlapping and area-fixed fields of renal cortex and medulla at ϫ400 magnification in each kidney specimen was calculated by using MetaMorph imaging software (Molecular Devices Co., Sunnyvale, CA) (33).…”

Section: Methodsmentioning

confidence: 99%

Leptospira santorosai Serovar Shermani Detergent Extract Induces an Increase in Fibronectin Production through a Toll-Like Receptor 2-Mediated Pathway

Tian

Hung

et al. 2011

Infect Immun

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Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-B, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition.

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“…Vitamin A-coupled liposomes almost completely resolved liver fibrosis and prolonged survival in rats with otherwise lethal dimethylnitrosamine-induced liver cirrhosis in a dose-and duration-dependent manner. Wang L et al [22] found RA reduced the amount of histologically detectable fibrosis produced by CCl 4 . Okuno et al [16,23] found the conflicting effects of RA on liver fibroses between two different animal models.…”

Section: Disscussionmentioning

confidence: 98%

Effect of all-trans retinoic acid on liver fibrosis induced by common bile duct ligation in rats

Wang

Dan

Jiang

2008

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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The aim of this study was to investigate the effect and possible mechanism of all-trans retinoic acid (ATRA) on liver fibrosis induced by common bile duct ligation (CBDL) in rats. Fifty-three female Wistar rats were randomly divided into 5 groups: sham operation group (group J, 5 animals) and groups A, B, C and D (12 animals in each group). The rats in groups A, B, C and D were subjected to CBDL to induce liver fibrosis, while those in group J to sham operation. From the 3rd week the rats in groups B, C and D respectively received daily administration of ATRA via gastric tube at three different doses [0.1, 1.5 and 7.5 mg/kg body weight (BW)]. Animals were sacrificed at 6th week. Rats' liver tissues were observed for pathologic changes under a light microscope. The protein levels of type I collagen (COL I), matrix metalloproteinase-2 (MMP2), MMP13 and tissue inhibitors of metalloproteinase-1 (TIMP-1) in liver tissues were determined by immunohistochemical techniques. The expression levels of TGF-beta1 and CTGF mRNA in liver tissues were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results showed that loss of normal hepatic architecture and formation of obvious fibrosis were observed in group A, while ATRA treatment for 4 weeks notably alleviated the pathological changes of hepatocytes. The expression of COL I and TIMP-1 proteins in group A was increased, while decreased in ATRA-treated CBDL groups (P<0.05). ATRA (1.5 and 7.5 mg/kg BW) reduced the expression levels of COL I protein more greatly than that of 0.1 mg/kg BW (P<0.05). ATRA treatment increased the protein levels of MMP2 and MMP13. The expression levels of TGF-beta1 and CTGF mRNA in group A were increased. In comparison with group A, the mRNA levels of TGF-beta1 and CTGF in ATRA-treated CBDL groups were significantly decreased (P<0.05). It was concluded that ATRA could inhibit CBDL-induced liver fibrosis in rats by suppressing the expression of TGF-beta1 and CTGF so as to diminish the inhibition of TIMP-1 on MMP2 and MMP13 and increase the activity of MMP2 and MMP13.

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Effects of retinoic acid on the development of liver fibrosis produced by carbon tetrachloride in mice

Cited by 62 publications

References 41 publications

Vitamin A deficiency injures liver parenchyma and alters the expression of hepatic extracellular matrix

Vitamin A deficiency injures liver parenchyma and alters the expression of hepatic extracellular matrix

Leptospira santorosai Serovar Shermani Detergent Extract Induces an Increase in Fibronectin Production through a Toll-Like Receptor 2-Mediated Pathway

Effect of all-trans retinoic acid on liver fibrosis induced by common bile duct ligation in rats

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