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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

ALDH1A1 mRNA expression and localization by in situ hybridization. Livers of VAA rats were used to detect rat ALDH1A1 mRNA expression (purple color). Green signals show nuclei counter stained by methyl green dye. Hepatocytes are notable by their large, round, methyl green-stained nuclei. Staining for ALDH1A1 mRNA was present throughout the parenchyma but was most intense around the portal tracts, including surrounding bile ducts (arrow, vehicle-treated liver). A sense RNA probe control is also illustrated. Magnification: × 200. Results for VAD liver were similar and therefore are not shown.
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Fig2: ALDH1A1 mRNA expression and localization by in situ hybridization. Livers of VAA rats were used to detect rat ALDH1A1 mRNA expression (purple color). Green signals show nuclei counter stained by methyl green dye. Hepatocytes are notable by their large, round, methyl green-stained nuclei. Staining for ALDH1A1 mRNA was present throughout the parenchyma but was most intense around the portal tracts, including surrounding bile ducts (arrow, vehicle-treated liver). A sense RNA probe control is also illustrated. Magnification: × 200. Results for VAD liver were similar and therefore are not shown.

Mentions: The localization of ALDH1A1 mRNA in the liver was determined by in situ hybridization (Figure 2). In VAA liver (shown) and VAD liver (similar and therefore not shown) ALDH1A1 mRNA signals were observed throughout the liver with relatively light staining in hepatocytes, which was somewhat weaker surrounding the central vein. Staining using the sense strand control showed only a light and relatively even distribution. Hepatocytes from vehicle-treated rats expressed ALDH1A1 mRNA in or around nuclei, while this was hardly observed in the RA- or LPS-treated groups. ALDH1A1 staining was more intense around vessels, especially in the periportal region, including around bile ducts, as shown in the vehicle-treated section. The sense control showed essentially no discrete staining. Conversely, there was no specific staining around blood vessels in the portal tracts. These results indicate that several types of liver cells express ALDH1A1 mRNA, including vascular epi- or endothelial cells and nonparenchymal cells within the portal tract. Sections from rats treated with LPS, both with and without RA, appeared to be more lightly stained. However, the distribution of ALDH1A1-positive cells was similar.Figure 2


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)

ALDH1A1 mRNA expression and localization by in situ hybridization. Livers of VAA rats were used to detect rat ALDH1A1 mRNA expression (purple color). Green signals show nuclei counter stained by methyl green dye. Hepatocytes are notable by their large, round, methyl green-stained nuclei. Staining for ALDH1A1 mRNA was present throughout the parenchyma but was most intense around the portal tracts, including surrounding bile ducts (arrow, vehicle-treated liver). A sense RNA probe control is also illustrated. Magnification: × 200. Results for VAD liver were similar and therefore are not shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: ALDH1A1 mRNA expression and localization by in situ hybridization. Livers of VAA rats were used to detect rat ALDH1A1 mRNA expression (purple color). Green signals show nuclei counter stained by methyl green dye. Hepatocytes are notable by their large, round, methyl green-stained nuclei. Staining for ALDH1A1 mRNA was present throughout the parenchyma but was most intense around the portal tracts, including surrounding bile ducts (arrow, vehicle-treated liver). A sense RNA probe control is also illustrated. Magnification: × 200. Results for VAD liver were similar and therefore are not shown.
Mentions: The localization of ALDH1A1 mRNA in the liver was determined by in situ hybridization (Figure 2). In VAA liver (shown) and VAD liver (similar and therefore not shown) ALDH1A1 mRNA signals were observed throughout the liver with relatively light staining in hepatocytes, which was somewhat weaker surrounding the central vein. Staining using the sense strand control showed only a light and relatively even distribution. Hepatocytes from vehicle-treated rats expressed ALDH1A1 mRNA in or around nuclei, while this was hardly observed in the RA- or LPS-treated groups. ALDH1A1 staining was more intense around vessels, especially in the periportal region, including around bile ducts, as shown in the vehicle-treated section. The sense control showed essentially no discrete staining. Conversely, there was no specific staining around blood vessels in the portal tracts. These results indicate that several types of liver cells express ALDH1A1 mRNA, including vascular epi- or endothelial cells and nonparenchymal cells within the portal tract. Sections from rats treated with LPS, both with and without RA, appeared to be more lightly stained. However, the distribution of ALDH1A1-positive cells was similar.Figure 2

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