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Magnesium Deficiency Induces the Emergence of Mast Cells in the Liver of Rats

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Mast cells, multifunctional effector cells of the immune system, are implicated in the pathogenesis of hepatic steatosis and fibrosis. Magnesium (Mg) deficiency was reported to increase triglyceride concentration in the liver, and to exacerbate the collagen deposition induced by carbon tetrachloride in the liver. Although Mg deficiency increases mast cells in the small intestine, the kidney and bone marrow, the effect of Mg deficiency on mast cells has not been clarified in the liver. We examined the emergence of mast cells in the liver of Sprague-Dawley rats given an Mg-deficient diet. Rats were fed a control diet or an Mg-deficient diet for 4 wk. Mg deficiency increased the levels of mRNA known to be expressed by mast cells in the liver; the mRNA of α- and β-chain high-affinity immunoglobulin E receptor (FcεR1α, FcεR1β), and the mRNA of mast cell protease 1 (Mcpt1), and mast cell protease 2 (Mcpt2). Histological observation showed that some mast cells were locally distributed around portal triads in the Mg-deficient group but mast cells were scarcely found in the control group. These results clearly indicate that Mg deficiency induces the emergence of mast cells around portal triads of the liver in Sprague-Dawley rats.
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560
J Nutr Sci Vitaminol, 59, 560–563, 2013
Although mast cells have been recognized to induce
allergic symptoms, mast cells are now widely accepted
to be multifunctional effector cells of the immune sys-
tem. In rats, mast cells mainly consist of the connective
tissue mast cells and the mucosal mast cells; the con-
nective tissue mast cells express rat mast cell protease-1
(rMCP-1) translated from Mcpt1 mRNA, and the muco-
sal mast cells express mast cell protease-2 (rMCP-2)
translated from Mcpt2 mRNA (1). These proteases are
known to have chymase activity (1).
In the liver, mast cells were suggested to contribute
to fibrosis (2, 3); mast cells secrete transforming growth
factor-
b
, tumor necrosis factor-
a
, vascular-endothelial
growth factor, and histamine, which directly or sec-
ondarily enhance fibrosis in the liver (4). Furthermore,
a recent report showed that the administration of chy-
mase inhibitor suppressed the steatosis induced by
methionine and choline deficiency, suggesting the con-
tribution of mast cells to steatosis (5).
Magnesium (Mg) deficiency was reported to increase
triglyceride concentration in the liver of rats given an
AIN93G-based diet (6) or a high-sucrose diet (7). Mg
deficiency was also reported to exacerbate the collagen
deposition induced by carbon-tetrachloride treatment
in the liver (8). Therefore, Mg deficiency is a stimulative
factor of hepatic fibrosis and steatosis possibly via its
effect on mast cells. Mg deficiency increases mast cells in
the duodenum (9, 10), the kidney (10), and bone mar-
row (11), but the effect of Mg deficiency on mast cells in
the liver has not been reported.
In the present study, we examined the effect of Mg
deficiency on the emergence of mast cells, and the
expression of makers of the connective tissue mast
cells, Mcpt1 mRNA, and the mucosal mast cells, Mcpt2
mRNA, in the rat liver.
Materials and Methods
Animals and diets. Twelve male-specific pathogen-
free Sprague-Dawley rats aged 4 wk were purchased
from Japan SLC, Inc. (Shizuoka, Japan) and cared for
according to the Guide for the Care and Use of Labora-
tory Animals (Animal Care Committee, Kyoto Univer-
sity). The rats were individually housed in stainless steel
cages in a temperature-, humidity- and light-controlled
room (24˚C, 60%, and 12-h light/dark cycle, respec-
tively). All rats were fed a control diet, the AIN-93G diet
(12), for a 5-d adaptation period. Then the animals were
divided into two groups of 6 rats given the control diet
or a low-Mg diet, an AIN-93G-based diet with Mg-free
AIN-93G mineral premix. The dietary Mg concentration
was 499 mg/kg and 44 mg/kg in the control diet and
the low-Mg diet, respectively.
The control rats were pair-fed to match the feed intake
of the rats given the low-Mg diet for 4 wk. The rats were
allowed free access to demineralized water during the
experiment.
Sample collection. Under isoflurane anesthesia, a
blood sample was obtained from the abdominal aorta
with a heparinized plastic syringe at the end of the
Note
Magnesium Deficiency Induces the Emergence of Mast Cells
in the Liver of Rats
Satoshi Takemoto, Akane Yamamoto, Shozo Tomonaga,
Masayuki Funaba and Tohru Matsui*
Division of Applied Biosciences, Graduate School Agriculture, Kyoto University, Kyoto 606–8502, Japan
(Received June 4, 2013)
Summary Mast cells, multifunctional effector cells of the immune system, are impli-
cated in the pathogenesis of hepatic steatosis and fibrosis. Magnesium (Mg) deficiency was
reported to increase triglyceride concentration in the liver, and to exacerbate the collagen
deposition induced by carbon tetrachloride in the liver. Although Mg deficiency increases
mast cells in the small intestine, the kidney and bone marrow, the effect of Mg deficiency
on mast cells has not been clarified in the liver. We examined the emergence of mast cells
in the liver of Sprague-Dawley rats given an Mg-deficient diet. Rats were fed a control diet
or an Mg-deficient diet for 4 wk. Mg deficiency increased the levels of mRNA known to be
expressed by mast cells in the liver; the mRNA of
a
- and
b
-chain high-affinity immunoglob-
ulin E receptor (Fc
e
R1
a
, Fc
e
R1
b
), and the mRNA of mast cell protease 1 (Mcpt1), and mast
cell protease 2 (Mcpt2). Histological observation showed that some mast cells were locally
distributed around portal triads in the Mg-deficient group but mast cells were scarcely found
in the control group. These results clearly indicate that Mg deficiency induces the emergence
of mast cells around portal triads of the liver in Sprague-Dawley rats.
Key Words mast cell, magnesium deficiency, liver, rats
* To whom correspondence should be addressed.
E-mail: matsui@kais.kyoto-u.ac.jp
Mast Cells in the Liver of Mg-Deficient Rats 561
experiment. Plasma was separated by centrifugation at
2,500 3g for 30 min at 4˚C. The plasma samples were
stored at 220˚C until analyses. The liver was promptly
excised and washed with ice-cold isotonic saline. One
part of the liver sample was placed in liquid nitrogen
and stored at 280˚C until analyses. The other part of
the liver sample was fixed in neutral 10% formalin solu-
tion (Wako Pure Chemical Industries, Ltd., Osaka,
Japan).
Analyses. The plasma samples were wet-digested
with trace element-grade HNO3 and H2O2 (Wako Pure
Chemical Industries, Ltd.). Then, we determined Mg
concentration in the plasma samples with an atomic
absorption spectrophotometer (AA-6600F; Shimadzu,
Kyoto, Japan).
Total RNA was extracted from the liver samples with
TRIzol reagents (Life Technologies, Carlsbad, CA)
according to the manufacturer’s protocol. Absorbance
at 260 nm was measured to quantify the RNA concen-
tration, and the ratio of absorbance at 260 nm to that
at 280 nm was simultaneously monitored to assess the
purity of RNA. Quantitative RT-PCR was carried out
using a SYBR premix Ex Taq II kit (TaKaRa, Otsu, Japan)
in a Rotor-Gene 6000 (Corbett Research, Mortlake, Aus-
tralia) (13, 14). The gene transcripts of
a
- and
b
-chain
high-affinity immunoglobulin E receptor (Fc
e
R1
a
,
Fc
e
R1
b
), Mcpt1, Mcpt2, and glyceraldehyde-3-phos-
phate dehydrogenase (Gapdh) were amplified by comple-
mentary DNA-specific primers (Table 1). The threshold
cycle (Ct) value was determined, and the abundance of
gene transcripts was calculated from the Ct value using
Gapdh as the corrected gene transcript.
Histological observation. Fixed samples of liver tissue
were embedded in paraffin. Sections were mounted on
glass slides and stained with toluidine blue. Cells con-
taining granules with metachromasy were identified as
mast cells in the liver (15).
Statistical analyses. Data are expressed as the
mean6SE. Differences between the control group and
the magnesium-deficient group were evaluated by Stu-
dent’s t test. Statistical significance was considered to be
p,0.05.
Results and Discussion
All rats given the low-Mg diet temporally showed
skin lesions in the ears and the tail (data not shown),
which is a typical sign of Mg deficiency in rats (14). No
skin lesion was observed in the control group through-
out the experiment. Plasma Mg concentration was
18.260.9 mg/L in the control rats and 7.760.3 mg/L
in the rats given the low-Mg diet; thus the low-Mg
diet significantly decreased plasma Mg concentration
(p,0.01). These results indicate that the low-Mg diet
induced Mg deficiency.
Mast cells and basophils express Fc
e
R1 in rodents
(16). The mRNA level of Fc
e
R1
a
was increased by Mg
deficiency in the liver (p,0.01) (Fig. 1). The mRNA level
of Fc
e
R1
b
was also increased by Mg deficiency in the
liver (p,0.05). The mRNA of Mcpt1 and Mcpt2 was not
detected in the liver of the control group; the Ct values
were more than 40 cycles in each control rat. These
results are consistent with a previous report indicating
that the mRNA of Mcpt1 and Mcpt2 were not detected
in the liver of healthy Sprague-Dawley rats (17). On
the other hand, the mRNA of Mcpt1 and Mcpt2 were
detected in all rats deficient for Mg and these Ct values
were 34.761.4 and 28.961.5, respectively.
In toluidine blue-stained sections, some cells contain-
ing granules with metachromasy were locally observed
around portal triads in the Mg-deficient group but these
cells were scarcely found in the control group (Fig. 2).
These results indicate that Mg deficiency induces the
emergence of mast cells around portal triads of the rat
liver.
In rats there are different main subsets of mast cells:
the connective tissue mast cells expressing rMCP-1
translated from Mcpt1 mRNA, and the mucosal mast
cells expressing rMCP-2 translated from Mcpt2 mRNA
(1). These proteases are known to have chymase activity
in rats (1). Chan et al. (18) reported that mast cells were
Table 1. Sequence of the PCR primers for amplification.
Genes Forward primer Reverse primer GenBank accession number
Fc
e
R1
a
5-TGTGTACTTGAACGTGATGCAA-35-TGTCTAAGACCACGTCAGCAG-3NM_012724
Fc
e
R1
b
5-CCCAAACCCACAAGAATCC-35-GCCATGTCTGCTGTGGTG-3NM_012845
Mcpt1 5-GCAAAATGCAGGCCCTACTA-35-GCGGGAGTGTGGAATAGACT-3NM_017145
Mcpt2 5-GGTCATCTGTGGTGGGTTTC-35-TGGATTCTCGCTTTCTCACA-3NM_172044
Gapdh 5-ACAACTTTGGCATCGTGGA-35-CTTCTGAGTGGCAGTGATGG-3NM_017008
Fig. 1. Effect of Mg deficiency on the mRNA level of
Fc
e
R1
a
and Fc
e
R1
b
in the rat liver. Data are expressed
as relative values with respect to the control group.
Mean6SE (n56). Significantly different from the con-
trol group (* p,0.05, ** p,0.01).
0
5
10
15
20
25
*
**
Relative mRNA level
FcεR1 FcεR1
Control
Mg deficiency
Takemoto S et al.
562
observed around portal triads of the liver in healthy
Australian albino Wistar rats, and that these mast cells
expressed rMCP-1 and/or rMCP-2, indicating that the
connective tissue mast cells and the mucosal mast cells
distribute around portal triads. Toluidine blue-staining
does not distinguish between the connective tissue mast
cells and the mucosal mast cells. However, Mg deficiency
induced mast cells in the liver and the distribution of
mast cell was restricted around portal triads. Further-
more, the mRNA of Mcpt1 and Mcpt2 were expressed
in the liver of Mg-deficient rats but not in the liver of
control rats. We conclude that Mg deficiency induces
the connective tissue mast cells and the mucosal mast
cells around portal triads. In addition, mRNA of Fc
e
R1
a
and Fc
e
R1
b
is possibly expressed by basophils slightly
infiltrating to the liver of control rats but the increase in
mast cells can explain the increasing expression of these
mRNA in the Mg-deficient rats.
Mast cells are suggested to be implicated in the patho-
genesis of hepatic fibrosis (2, 3). Mg deficiency itself
does not affect collagen concentration in the liver but
exacerbates the collagen deposition induced by a treat-
ment with carbon-tetrachloride (8). It is likely that the
emergence of mast cells does not solely induce hepatic
fibrosis in the Mg-deficient rats. Liver fibrosis is a wound-
healing response to chronic injury, which is charac-
terized by excessive deposition of collagen. Thus, Mg
deficiency possibly exacerbates the collagen deposition
through inducing the emergence of mast cells when the
liver is damaged.
Histological observation indicated that enlarged vac-
uoles, probably consisting of fat, were located close to
the portal triad of the Mg-deficient rats but such vacu-
oles were not observed in the control rats (Fig. 2). These
results are partly consistent with previous reports indi-
cating that Mg deficiency increased triglyceride concen-
tration in the liver (6, 7). A recent report indicated that
a methionine- and choline-deficient diet increased mast
cells, lipid accumulation, and chymase activity in the
liver of hamsters, while the treatment with a chymase
inhibitor dramatically attenuated the lipid accumula-
tion; thus the inhibition of mast-cell activity attenu-
ates hepatic steatosis induced by the methionine- and
choline-deficient diet (5). Hamster chymase efficiently
converts angiotensin I to angiotensin II, which has been
hypothesized to induce hepatic steatosis (5). Rat chy-
mase, rMCP-1, also activates angiotensin II production
(19); Mg deficiency increases chymase expression at the
transcription level by mast cells in the rat liver, which
possibly increases triglyceride accumulation.
The present experiment indicated that Mg deficiency
increased the number of mast cells and the mRNA
expression of chymases in the liver. Further study is
necessary for clarifying the involvement of hepatic mast
cells and chymase in the effect of Mg deficiency on the
liver, i.e., the increase in lipid accumulation and the
exacerbation of collagen deposition.
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Fig 2. Representative histological appearance of toluidine blue staining of liver sections from control (A) and Mg-deficient
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m
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Mast Cells in the Liver of Mg-Deficient Rats 563
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... In PEM rats infected with T. spiralis, the impaired systemic and mucosal immune response to infection was also associated with fewer mast cells in airway and intestinal mucosae (89). During magnesium deficiency, which exacerbates liver fibrosis in a rat model, depletion of mast cell numbers in the ileum, kidney, and bone marrow occurred alongside increased mast cell accumulation and functional gene expression (α-and β-chain high-affinity IgE receptors, mast cell protease 1 and 2) in the liver (92). ...
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Undernutrition affects millions of children in low- and middle-income countries (LMIC) and underlies almost half of all deaths among children under 5 years old. The growth deficits that characterize childhood undernutrition (stunting and wasting) result from simultaneous underlying defects in multiple physiological processes, and current treatment regimens do not completely normalize these pathways. Most deaths among undernourished children are due to infections, indicating that their anti-pathogen immune responses are impaired. Defects in the body's first-line-of-defense against pathogens, the innate immune system, is a plausible yet understudied pathway that could contribute to this increased infection risk. In this review, we discuss the evidence for innate immune cell dysfunction from cohort studies of childhood undernutrition in LMIC, highlighting knowledge gaps in almost all innate immune cell types. We supplement these gaps with insights from relevant experimental models and make recommendations for how human and animal studies could be improved. A better understanding of innate immune function could inform future tractable immune-targeted interventions for childhood undernutrition to reduce mortality and improve long-term health, growth and development.
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Despite the development of a number of vaccines for COVID-19, there remains a need for prevention and treatment of the virus SARS-CoV-2 and the ensuing disease COVID-19. This report discusses the key elements of SARS-CoV-2 and COVID-19 that can be readily treated: viral entry, the immune system and inflammation, and the cytokine storm. It is shown that the essential nutrients zinc, ω-3 polyunsaturated fatty acids (PUFAs), vitamin D and magnesium provide the ideal combination for prevention and treatment of COVID-19: prevention of SARS-CoV-2 entry to host cells, prevention of proliferation of SARS-CoV-2, inhibition of excessive inflammation, improved control of the regulation of the immune system, inhibition of the cytokine storm, and reduction in the effects of acute respiratory distress syndrome (ARDS) and associated non-communicable diseases. It is emphasized that the non-communicable diseases associated with COVID-19 are inherently more prevalent in the elderly than the young, and that the maintenance of sufficiency of zinc, ω-3 PUFAs, vitamin D and magnesium is essential for the elderly to prevent the occurrence of non-communicable diseases such as diabetes, cardiovascular diseases, lung diseases and cancer. Annual checking of levels of these essential nutrients is recommended for those over 65 years of age, together with appropriate adjustments in their intake, with these services and supplies being at government cost. The cost:benefit ratio would be huge as the cost of the nutrients and the testing of their levels would be very small compared with the cost savings of specialists and hospitalization.
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Magnesium (Mg) deficiency is an actual dietary problem in developed countries including Japan. We have studied mineral nutrition centered on Mg using laboratory animals and cultured cells. We evaluated Mg absorption from marine algae and drinking water, and the results indicated that the forms of soluble Mg and sojourn time of Mg in the digestive tract affected Mg absorption. Mg deficiency induced the appearance of mast cells in the liver, a phenomenon that has been linked to the pathogenesis of non-alcoholic fatty liver disease. Comprehensive and non-targeted analysis of metabolites clarified that Mg deficiency disturbs some aspects of metabolism in both the liver and hepatic cell models. Comprehensive and targeted analysis of metals indicated that Mg deficiency affected the hepatic concentration of 8 metals including molybdenum. Mg deficiency increased the hepatic zinc concentration through increased expression of the zinc transporter (Zip14) and metallothionein genes. Mg deficiency increased the hepatic iron concentration by the unresponsive expression of hepcidin gene as a result of BMP signal blunting. Activin B and interleukin-1β enhanced the expression of hepcidin, which is probably one aspect of the pathogenesis of inflammatory anemia.
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Toluidine blue is a basic thiazine metachromatic dye with high affinity for acidic tissue components, thereby staining tissues rich in DNA and RNA. It has found wide applications both as vital staining in living tissues and as a special stain owing to its metachromatic property. Toluidine blue has been used in vivo to identify dysplasia and carcinoma of the oral cavity. Use of toluidine blue in tissue sections is done with the aim to highlight components, such as mast cells granules, mucins, and cartilage. This article provides an overview on chemistry, technique, and the various applications of toluidine blue.
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The AIN-93 rodent diets were formulated to substitute for the previous version (AIN-76A) and to improve the performance of animals that consume them. They are called AIN-93G, formulated for growth, and AIN-93M, for maintenance. Major changes included substituting cornstarch for sucrose and soybean oil for corn oil and increasing the amount in order to supply both essential fatty acids (linoleic and linolenic). L-Cystine was substituted for DL-methionine to supplement the casein component. The mineral mix was reformulated to lower the amounts of phosphorus, manganese and chromium, to increase the amount of selenium, and to add molybdenum, silicon, fluoride, nickel, boron, lithium and vanadium. The amounts of vitamins E, K-1 and B-12 were increased over those in the AIN-76A vitamin mix. The AIN-93G diet contains 200 g of casein and 70 g of soybean oil/kg diet. The maintenance diet (AIN-93M) contains 140 g of casein and 40 g of soybean oil/kg diet. The 1993 diets have a better balance of essential nutrients than the 1976 diet and are better choices for studies with laboratory rodents.
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Aim: Chymase plays a role in the augmentation of angiotensin II formation, which is involved in liver fibrosis. The therapeutic effects of a chymase inhibitor, TY-51469, on established hepatic steatosis and fibrosis were investigated in a model of developed non-alcoholic steatohepatitis. Methods: Hamsters were fed a normal diet or methionine- and choline-deficient (MCD) diet for 12 weeks. Then, treatment with TY-51469 (1 mg/kg per day) or placebo was initiated, and the treatment was continued concurrently with the MCD diet for an additional 12 weeks. Results: At 12 weeks after initiating the MCD diet, marked hepatic steatosis and fibrosis were observed in MCD diet-fed hamsters. Malondialdehyde and gene expression levels of collagen I, collagen III, α-smooth muscle actin (α-SMA) and Rac-1 in liver extracts were also increased in the MCD-diet-fed hamsters at 12 weeks. At 24 weeks, hepatic steatosis and fibrosis were more prominent in the placebo-treated hamsters that were fed the MCD-diet for 24 weeks versus 12 weeks. Hamsters treated with TY-51469 for 12 weeks after being on a 12-week MCD diet had significant ameliorations in both hepatic steatosis and fibrosis, and there were no significant differences compared to normal diet-fed hamsters. There were significant augmentations in angiotensin II and malondialdehyde, and gene expressions of collagen I, collagen III, α-SMA and Rac-1 in the placebo-treated hamsters at 24 weeks; however, these levels were reduced to normal levels in the TY-51469-treated hamsters. Conclusion: TY-51469 not only prevented the progression of hepatic steatosis and fibrosis, but also ameliorated hepatic steatosis and fibrosis.
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Mast cells are known to be present in human liver but their distribution and density in normal livers and in chronic liver diseases have not previously been examined. In this study, we quantified mast cell numbers and examined their distribution in percutaneous biopsy specimens from normal livers (n = 8) and in two chronic progressive liver diseases: primary biliary cirrhosis (PBC) (n = 40) and alcoholic liver disease (n = 33). We compared differences in mast cell density between these two forms of chronic liver disease because it had been suggested that mast cells may play a role in the development of liver fibrosis, particularly in patients with chronic cholestatic liver disease who frequently have increased plasma histamine levels. Mast cells were identified by immunohistochemistry using a specific monoclonal antibody (AA1) raised against mast cell tryptase after an initial study showed this to be more sensitive for the detection of mast cells than the conventional histochemical stain, toluidine blue. Our results showed that small numbers of mast cells (3.9 ± 3.3/mm2) are present within the portal tracts and sinusoids of normal livers. In progressive chronic liver disease, increased numbers of mast cells were present, which correlated with the increasing amounts of liver fibrosis present. We found significantly more mast cells in the PBC group compared with the alcoholic group for a given amount of fibrosis. Our findings suggest that mast cells and their mediators may play a role in liver fibrogenesis. (HEPATOLOGY 1995; 22:1175–1181.).
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 There is evidence that mast cells are involved in a number of pathophysiological processes. The significance of mast cells in hepatic fibrosis was examined in 28 patients with histologically normal livers, 34 with acute liver diseases, 51 with chronic liver diseases, and 59 with cholestatic biliary diseases, using immunostaining of the mast cell-specific proteinase, tryptase. Mast cells that were positive for tryptase and for chymase were significantly increased in frequency in fibrotic portal tracts and fibrous septa, particularly in cholestatic/biliary diseases. Mast cells were also increased in frequency around the fibrotic septal and intrahepatic large bile ducts and peribiliary glands of biliary diseases. However, they were less common or even rare in the sclerotic bile ducts and in scarred portal or septal fibrosis. More than half of these more numerous mast cells were positive for histamine, and some were also positive for basic fibroblast growth factor. These two substances were detectable by immunoelectron microscopic in the cytoplasmic granules of mast cells. In contrast, mast cell numbers were not significantly increased in acute viral or drug-induced hepatitis, or in zones 2 and 3 of the hepatic acinus with respect to pericellular and perivenular fibrosis in chronic liver diseases. These findings suggest that mast cells increase in number in cholestatic/biliary diseases, and to a lesser degree in chronic liver diseases, and are involved in the active fibrous enlargement of portal tract and fibrous septa formation and also in the fibrosis of the intrahepatic bile ducts as they display fibrosis-promoting factors such as tryptase, fibroblast growth factor and histamine.
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Mg deficiency increases the concentration of Zn in the liver. We investigated the effect of Mg deficiency on the expression of Zn-regulating factors such as Zn transporters and metallothionein (MT) in the rat liver. Because Ca deficiency alleviates some of the effects of Mg deficiency, we also investigated the interactions associated with Ca and Mg deficiencies. Growing male rats were given a control diet, a Mg-deficient diet, a Ca-deficient diet and a Mg- and Ca-deficient diet for 3 weeks. Mg and Ca deficiencies additively increased the mRNA levels of MT-1 and MT-2, the MT protein concentration and the concentration of Zn in the liver. The hepatic mRNA level of Zip14 increased with Mg deficiency but not with Ca deficiency. The dietary treatments did not affect the mRNA levels of other Zn transporters such as Zip1, Zip5, ZnT1, ZnT5 and ZnT6 in the liver. Ca deficiency was found to decrease the amount of femoral Zn and increase serum Zn concentration. This did not occur in the case of Mg deficiency. These results suggest that Mg deficiency enhances hepatic Zn uptake by the up-regulation of Zip14 expression and increases hepatic Zn concentration, leading to the enhancement of MT expression. Ca deficiency causes a transfer of Zn from the bone to the liver, which increases hepatic Zn concentration and, in turn, up-regulates the expression of MT. Because Mg and Ca deficiencies increase hepatic Zn concentration and increase MT expression by different mechanisms, their effects are additive.
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Previous studies revealed that bone morphogenetic protein (BMP) induces commitment to the adipocyte lineage in pluripotent stem cells. The present study explored the role of endogenous BMP activity in 3T3-L1 preadipocytes. The expression of phospho-Smad1/5/8 was monitored because BMP transmits its signal through Smad1/5/8 phosphorylation. Phosphorylated Smad1/5/8 was higher in proliferating preadipocytes, and lower in differentiating adipocytes after removing differentiation inducers. Reporter assays revealed that dorsomorphin predominantly inhibits the BMP pathway but not the structurally related TGF-beta/activin pathway. The addition of dorsomorphin to the culture medium prior to treatment with differentiation inducers impaired lipid accumulation in 3T3-L1 cells. The present study indicated that activation of BMP signaling in preadipocytes is required for these cells to initiate the adipogenic program.
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We investigated the effects of ascorbic acid (AsA) supplementation on lipid peroxidation and the lipid content in the liver and serum of magnesium (Mg)-deficient rats. Eighteen 3-week-old male Sprague-Dawley strain rats were divided into 3 groups and maintained on a control diet (C group), a low-Mg diet (D group), or a low-Mg diet supplemented with AsA (DA group) for 42 d. At the end of this period, the final body weight, weight gain, and serum Mg concentrations were significantly decreased in the Mg-deficient rats. Further, dietary AsA supplementation had no effect on the growth, serum Mg concentration, Mg absorption, and Mg retention. The serum concentration of AsA was significantly lower in the D group than in the C group but was unaltered in the DA group. The levels of phosphatidylcholine hydroperoxide (PCOOH) in the serum and of triglycerides (TGs) and total cholesterol (TC) in the serum and liver were significantly higher in the D group than in the C group. The serum PCOOH, liver TG, and liver TC levels were decreased in the DA group. These results indicate that Mg deficiency increases the AsA requirement of the body and that AsA supplementation normalizes the serum levels of PCOOH and the liver lipid content in Mg-deficient rats, without altering the Mg status.
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Rats were maintained on a magnesium-deficient diet for 1 to 5 weeks to study the mast cell (MC) populations in their duodenum and kidney. A marked increase of intestinal subepithelial mast cells was observed in these animals as compared with normal controls. The cells in both groups showed an identical reaction for mucopolysaccharides but the 5-hydroxytryptamine content tended to be higher in the cells of magnesium-deficient animals. Proliferation of MC was also observed in the renal cortex of the magnesium-deficient rats. This finding is significant because MC are known to be virtually absent from normal kidneys. Magnesium deprivation resulted in numerous MC not only in the intertubular spaces but also within the glomeruli. Possible correlations between these and other pertinent observations are discussed with regard to certain renal diseases. The discussion is extended to the possible mechanism through which magnesium could influence secretory processes in MC.
Article
Comparative counts of Alcian Blue-Basic Fuchsin-stained mast cells of the facial skin and bone marrow have been made in young rats of different sexes and strains, fed a diet deficient in magnesium (0.8 to 1 mg/100 g dry weight) for 4 weeks. Normal rats fed a magnesium-supplemented diet (65 mg/100 g dry weight) had about three times as many mast cells in the tibial metaphysis as in the facial skin. In both males and females fed the Mg-deficient diet, the marrow mast cells increased five to six times, while their number was concomitantly decreased in the skin. The marrow mast cells became also polymorphic, an indication of a possible preferential renewal site. Gonadectomy in the males had no effect on the above pattern. The administration of large doses of testosterone to males and estradiol to females depressed the mast cell population increase in the bone marrow and at the same time, moderated the loss of skin mast cells.