Downregulation of prostaglandin E 2 is involved in hindgut mucosal damage in lactating goats fed a high‐concentrate diet
New Findings What is the central question of this study? A high‐concentrate (HC) diet results in damage to the hindgut mucosa. The aim of the study was to investigate the status of epithelial proliferation in the hindgut mucosa of goats with subacute ruminal acidosis and, simultaneously, to evaluate...
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Published in | Experimental physiology Vol. 101; no. 2; pp. 272 - 281 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.02.2016
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Abstract | New Findings
What is the central question of this study?
A high‐concentrate (HC) diet results in damage to the hindgut mucosa. The aim of the study was to investigate the status of epithelial proliferation in the hindgut mucosa of goats with subacute ruminal acidosis and, simultaneously, to evaluate prostaglandin E
2
synthesis and the downstream signalling pathways.
What is the main finding and its importance?
The downregulation of local prostaglandin E
2
synthesis and its downstream signalling pathway are involved in the process of inhibiting epithelial proliferation in the hindgut epithelium of HC‐fed goats. Our results provide new insight into the relationship between abnormal fermentation in the hindgut and damage to the intestinal mucosal barrier.
Our previous data demonstrated that feeding a high‐concentrate (HC) diet to lactating goats for a long time causes severe damage to the hindgut mucosa and parallels the activation of cell apoptosis and local oxidative stress. In the present study, changes in production of prostaglandin E
2
(PGE
2
) and its signalling pathway were evaluated in the process of epithelial barrier disruption in the hindgut. Twelve goats in mid‐lactation were randomly assigned to either a HC diet group or a low‐concentrate (LC) diet group for 10 weeks. Cell proliferation markers, cyclooxygenase‐2 activity, PGE
2
content and the relative signalling pathway, including CREB and AKT, were analysed by enzyme‐linked immunosorbent assay and Western blot, respectively. The mRNA and protein expressions of MKI67 and CCND2 (two proliferation markers) were significantly decreased in the caecal mucosa of HC‐ compared with LC‐fed goats (
P
< 0.05). The protein content of interleukin‐10 and β‐defensin in the caecal mucosa was also downregulated in HC‐fed goats (
P
< 0.05). The HC‐fed goats showed a tendency to a decrease in cyclooxygenase‐2 enzyme activity (
P
= 0.081) and a significant decrease of local PGE
2
content and EP4 (PGE
2
receptor) protein expression in caecal mucosa (
P
< 0.05). Moreover, the protein abundance of p‐CREB (
P
= 0.069) and p‐AKT (
P
< 0.05) and the mRNA expression of epidermal growth factor receptor (
P
< 0.05) were downregulated in caecal mucosa of HC‐ compared with LC‐fed goats. These results indicate that a reduction in epithelial cell proliferation was partly responsible for the damage to the epithelial barrier, which might be associated with the downregulation of PGE
2
synthesis and its downstream signalling pathway. |
---|---|
AbstractList | New Findings
What is the central question of this study?
A high‐concentrate (HC) diet results in damage to the hindgut mucosa. The aim of the study was to investigate the status of epithelial proliferation in the hindgut mucosa of goats with subacute ruminal acidosis and, simultaneously, to evaluate prostaglandin E
2
synthesis and the downstream signalling pathways.
What is the main finding and its importance?
The downregulation of local prostaglandin E
2
synthesis and its downstream signalling pathway are involved in the process of inhibiting epithelial proliferation in the hindgut epithelium of HC‐fed goats. Our results provide new insight into the relationship between abnormal fermentation in the hindgut and damage to the intestinal mucosal barrier.
Our previous data demonstrated that feeding a high‐concentrate (HC) diet to lactating goats for a long time causes severe damage to the hindgut mucosa and parallels the activation of cell apoptosis and local oxidative stress. In the present study, changes in production of prostaglandin E
2
(PGE
2
) and its signalling pathway were evaluated in the process of epithelial barrier disruption in the hindgut. Twelve goats in mid‐lactation were randomly assigned to either a HC diet group or a low‐concentrate (LC) diet group for 10 weeks. Cell proliferation markers, cyclooxygenase‐2 activity, PGE
2
content and the relative signalling pathway, including CREB and AKT, were analysed by enzyme‐linked immunosorbent assay and Western blot, respectively. The mRNA and protein expressions of MKI67 and CCND2 (two proliferation markers) were significantly decreased in the caecal mucosa of HC‐ compared with LC‐fed goats (
P
< 0.05). The protein content of interleukin‐10 and β‐defensin in the caecal mucosa was also downregulated in HC‐fed goats (
P
< 0.05). The HC‐fed goats showed a tendency to a decrease in cyclooxygenase‐2 enzyme activity (
P
= 0.081) and a significant decrease of local PGE
2
content and EP4 (PGE
2
receptor) protein expression in caecal mucosa (
P
< 0.05). Moreover, the protein abundance of p‐CREB (
P
= 0.069) and p‐AKT (
P
< 0.05) and the mRNA expression of epidermal growth factor receptor (
P
< 0.05) were downregulated in caecal mucosa of HC‐ compared with LC‐fed goats. These results indicate that a reduction in epithelial cell proliferation was partly responsible for the damage to the epithelial barrier, which might be associated with the downregulation of PGE
2
synthesis and its downstream signalling pathway. |
Author | Han, Zhengqiang Cong, Rihua Zhao, Ruqian Tao, Shiyu Duanmu, Yongqian Tian, Jing Dong, Haibo Ni, Yingdong |
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CitedBy_id | crossref_primary_10_1016_j_psj_2023_102782 crossref_primary_10_1080_19490976_2022_2039048 crossref_primary_10_1186_s12917_019_2031_5 crossref_primary_10_3389_fmicb_2017_01764 crossref_primary_10_1080_1828051X_2021_1873706 |
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What is the central question of this study?
A high‐concentrate (HC) diet results in damage to the hindgut mucosa. The aim of the study was to... |
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Title | Downregulation of prostaglandin E 2 is involved in hindgut mucosal damage in lactating goats fed a high‐concentrate diet |
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