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Inflammation rapidly modulates the expression of ALDH1A1 (RALDH1) and vimentin in the liver and hepatic macrophages of rats in vivo.

Ito K, Zolfaghari R, Hao L, Ross AC - Nutr Metab (Lond) (2014)

Bottom Line: ALDH1A1 protein exhibited diffuse staining in hepatocytes, with greater intensity in the periportal region including surrounding bile ducts.Alpha-smooth muscle actin staining was intense around blood vessels, but did not change after LPS or RA, nor overlap with staining for vimentin.In addition, the rapid strong response of vimentin expression after treatment with LPS suggests that increased vimentin may be a useful marker of early hepatic inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802 USA.

ABSTRACT

Background: Members of the ALDH1 protein family, known as retinal dehydrogenases (RALDH), produce retinoic acid (RA), a metabolite of vitamin A, and may also oxidize other lipid aldehydes. Of three related ALDH1 genes, ALDH1A1 is most highly expressed in liver. ALDH1A1 is also rapidly gaining importance as a stem cell marker. We hypothesized that ALDH1A1 may have a broad cellular distribution in the liver, and that its expression may be regulated by RA and perturbed by inflammation.

Methods: Studies were conducted in vitamin A-deficient and -adequate rats that were further treated with all-trans-RA or lipopolysaccharide (LPS) to induce a state of moderate inflammation. RALDH1A1 expression was determined by quantitative PCR and RALDH1, as well as marker gene expression, was determined by immunocytochemical methods.

Results: Inflammation reduced ALDH1A1 mRNA in whole liver regardless of the level of vitamin A in the diet (P < 0.05), while treatment with RA reduced ALDH1A1 expression only in chow-fed rats. ALDH1A1 protein exhibited diffuse staining in hepatocytes, with greater intensity in the periportal region including surrounding bile ducts. Six h after administration of LPS, portal region macrophages were more numerous and some of these cells contained ALDH1A1. Vimentin, which was used as a marker for stellate cells and fibroblasts, was increased by LPS, P = 0.011 vs. without LPS, in both ED1 (CD68)-positive macrophages and fibroblastic stellate-like cells in the parenchyma as well as portal regions. Alpha-smooth muscle actin staining was intense around blood vessels, but did not change after LPS or RA, nor overlap with staining for vimentin.

Conclusions: Acute inflammation rapidly downregulates ALDH1A1 expression in whole liver while increasing its expression in periportal macrophages. Changes in ALDH1A1 expression appear to be part of the early acute-phase inflammatory response, which has been shown to alter the expression of other retinoid homeostatic genes. In addition, the rapid strong response of vimentin expression after treatment with LPS suggests that increased vimentin may be a useful marker of early hepatic inflammation.

No MeSH data available.


Related in: MedlinePlus

Relative mRNA expression of vimentin in VAA and VAD diet rat liver. Vimentin mRNA in VAA (black bars) or VAD (grey bars) rats, determined by qRT-PCR. Normalized values were expressed as the mean ± SEM of n = 5 (n = 4 for VAD vehicle)/group, with the VAA control group set to 1.0. Diet was a significant main effect, P <0.01, and LPS treatment marginally increased vimentin mRNA expression, P = 0.062 compared to the VAA vehicle control group.
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Fig7: Relative mRNA expression of vimentin in VAA and VAD diet rat liver. Vimentin mRNA in VAA (black bars) or VAD (grey bars) rats, determined by qRT-PCR. Normalized values were expressed as the mean ± SEM of n = 5 (n = 4 for VAD vehicle)/group, with the VAA control group set to 1.0. Diet was a significant main effect, P <0.01, and LPS treatment marginally increased vimentin mRNA expression, P = 0.062 compared to the VAA vehicle control group.

Mentions: The increase in vimentin protein observed by histology in Figure 5 was accompanied by a small increase in vimetin mRNA in total liver tissue (Figure 7). Regardless of the treatment group, vimentin mRNA was higher in the liver of VAD rats than VAA rats (diet effect, P < 0.01). Average values for vimentin mRNA after LPS treatment were higher in both VAD and VAA groups, consistent with the protein staining results shown in Figure 5g, although this was marginally significant (P = 0.062) only in the VAA group.Figure 7


Inflammation rapidly modulates the expression of ALDH1A1 (RALDH1) and vimentin in the liver and hepatic macrophages of rats in vivo.

Ito K, Zolfaghari R, Hao L, Ross AC - Nutr Metab (Lond) (2014)

Relative mRNA expression of vimentin in VAA and VAD diet rat liver. Vimentin mRNA in VAA (black bars) or VAD (grey bars) rats, determined by qRT-PCR. Normalized values were expressed as the mean ± SEM of n = 5 (n = 4 for VAD vehicle)/group, with the VAA control group set to 1.0. Diet was a significant main effect, P <0.01, and LPS treatment marginally increased vimentin mRNA expression, P = 0.062 compared to the VAA vehicle control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4414379&req=5

Fig7: Relative mRNA expression of vimentin in VAA and VAD diet rat liver. Vimentin mRNA in VAA (black bars) or VAD (grey bars) rats, determined by qRT-PCR. Normalized values were expressed as the mean ± SEM of n = 5 (n = 4 for VAD vehicle)/group, with the VAA control group set to 1.0. Diet was a significant main effect, P <0.01, and LPS treatment marginally increased vimentin mRNA expression, P = 0.062 compared to the VAA vehicle control group.
Mentions: The increase in vimentin protein observed by histology in Figure 5 was accompanied by a small increase in vimetin mRNA in total liver tissue (Figure 7). Regardless of the treatment group, vimentin mRNA was higher in the liver of VAD rats than VAA rats (diet effect, P < 0.01). Average values for vimentin mRNA after LPS treatment were higher in both VAD and VAA groups, consistent with the protein staining results shown in Figure 5g, although this was marginally significant (P = 0.062) only in the VAA group.Figure 7

Bottom Line: ALDH1A1 protein exhibited diffuse staining in hepatocytes, with greater intensity in the periportal region including surrounding bile ducts.Alpha-smooth muscle actin staining was intense around blood vessels, but did not change after LPS or RA, nor overlap with staining for vimentin.In addition, the rapid strong response of vimentin expression after treatment with LPS suggests that increased vimentin may be a useful marker of early hepatic inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802 USA.

ABSTRACT

Background: Members of the ALDH1 protein family, known as retinal dehydrogenases (RALDH), produce retinoic acid (RA), a metabolite of vitamin A, and may also oxidize other lipid aldehydes. Of three related ALDH1 genes, ALDH1A1 is most highly expressed in liver. ALDH1A1 is also rapidly gaining importance as a stem cell marker. We hypothesized that ALDH1A1 may have a broad cellular distribution in the liver, and that its expression may be regulated by RA and perturbed by inflammation.

Methods: Studies were conducted in vitamin A-deficient and -adequate rats that were further treated with all-trans-RA or lipopolysaccharide (LPS) to induce a state of moderate inflammation. RALDH1A1 expression was determined by quantitative PCR and RALDH1, as well as marker gene expression, was determined by immunocytochemical methods.

Results: Inflammation reduced ALDH1A1 mRNA in whole liver regardless of the level of vitamin A in the diet (P < 0.05), while treatment with RA reduced ALDH1A1 expression only in chow-fed rats. ALDH1A1 protein exhibited diffuse staining in hepatocytes, with greater intensity in the periportal region including surrounding bile ducts. Six h after administration of LPS, portal region macrophages were more numerous and some of these cells contained ALDH1A1. Vimentin, which was used as a marker for stellate cells and fibroblasts, was increased by LPS, P = 0.011 vs. without LPS, in both ED1 (CD68)-positive macrophages and fibroblastic stellate-like cells in the parenchyma as well as portal regions. Alpha-smooth muscle actin staining was intense around blood vessels, but did not change after LPS or RA, nor overlap with staining for vimentin.

Conclusions: Acute inflammation rapidly downregulates ALDH1A1 expression in whole liver while increasing its expression in periportal macrophages. Changes in ALDH1A1 expression appear to be part of the early acute-phase inflammatory response, which has been shown to alter the expression of other retinoid homeostatic genes. In addition, the rapid strong response of vimentin expression after treatment with LPS suggests that increased vimentin may be a useful marker of early hepatic inflammation.

No MeSH data available.


Related in: MedlinePlus