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Liver injury in a preclinical model of short bowel syndrome is associated with impaired autophagy
by
Alligood, Daniel M.
, Mayse, Evan
, Park, Alex
, Rubin, Deborah C.
, Warner, Brad W.
, Kim, Jae-Sung
, Swanson, Kerry
, Alvarado, David M.
, Davidson, Nicholas O.
, Pyarali, Naima
, Liu, Xiuli
, Guo, Jun
in
1-Phosphatidylinositol 3-kinase
/ 631/80/39
/ 692/4020/1503/1607
/ AKT protein
/ Animal models
/ Animals
/ Autophagy
/ Disease Models, Animal
/ Endoplasmic reticulum
/ Endoplasmic Reticulum Stress
/ ErbB protein
/ Female
/ Females
/ Gene expression
/ Hepatocytes
/ Hepatocytes - metabolism
/ Hepatocytes - pathology
/ Histology
/ Humanities and Social Sciences
/ Immunohistochemistry
/ Inflammation
/ Intestinal failure associated liver disease
/ Intestine
/ Kinases
/ Liver
/ Liver - injuries
/ Liver - metabolism
/ Liver - pathology
/ Liver cirrhosis
/ Liver diseases
/ Liver Diseases - etiology
/ Liver Diseases - metabolism
/ Liver Diseases - pathology
/ Male
/ Males
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ Nutrition
/ Oxidative Stress
/ Parenteral nutrition
/ Protein expression
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Sexes
/ Short bowel syndrome
/ Short Bowel Syndrome - complications
/ Short Bowel Syndrome - metabolism
/ Short Bowel Syndrome - pathology
/ Small intestine
/ Statistical analysis
/ Surgery
2025
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Liver injury in a preclinical model of short bowel syndrome is associated with impaired autophagy
by
Alligood, Daniel M.
, Mayse, Evan
, Park, Alex
, Rubin, Deborah C.
, Warner, Brad W.
, Kim, Jae-Sung
, Swanson, Kerry
, Alvarado, David M.
, Davidson, Nicholas O.
, Pyarali, Naima
, Liu, Xiuli
, Guo, Jun
in
1-Phosphatidylinositol 3-kinase
/ 631/80/39
/ 692/4020/1503/1607
/ AKT protein
/ Animal models
/ Animals
/ Autophagy
/ Disease Models, Animal
/ Endoplasmic reticulum
/ Endoplasmic Reticulum Stress
/ ErbB protein
/ Female
/ Females
/ Gene expression
/ Hepatocytes
/ Hepatocytes - metabolism
/ Hepatocytes - pathology
/ Histology
/ Humanities and Social Sciences
/ Immunohistochemistry
/ Inflammation
/ Intestinal failure associated liver disease
/ Intestine
/ Kinases
/ Liver
/ Liver - injuries
/ Liver - metabolism
/ Liver - pathology
/ Liver cirrhosis
/ Liver diseases
/ Liver Diseases - etiology
/ Liver Diseases - metabolism
/ Liver Diseases - pathology
/ Male
/ Males
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ Nutrition
/ Oxidative Stress
/ Parenteral nutrition
/ Protein expression
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Sexes
/ Short bowel syndrome
/ Short Bowel Syndrome - complications
/ Short Bowel Syndrome - metabolism
/ Short Bowel Syndrome - pathology
/ Small intestine
/ Statistical analysis
/ Surgery
2025
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Liver injury in a preclinical model of short bowel syndrome is associated with impaired autophagy
by
Alligood, Daniel M.
, Mayse, Evan
, Park, Alex
, Rubin, Deborah C.
, Warner, Brad W.
, Kim, Jae-Sung
, Swanson, Kerry
, Alvarado, David M.
, Davidson, Nicholas O.
, Pyarali, Naima
, Liu, Xiuli
, Guo, Jun
in
1-Phosphatidylinositol 3-kinase
/ 631/80/39
/ 692/4020/1503/1607
/ AKT protein
/ Animal models
/ Animals
/ Autophagy
/ Disease Models, Animal
/ Endoplasmic reticulum
/ Endoplasmic Reticulum Stress
/ ErbB protein
/ Female
/ Females
/ Gene expression
/ Hepatocytes
/ Hepatocytes - metabolism
/ Hepatocytes - pathology
/ Histology
/ Humanities and Social Sciences
/ Immunohistochemistry
/ Inflammation
/ Intestinal failure associated liver disease
/ Intestine
/ Kinases
/ Liver
/ Liver - injuries
/ Liver - metabolism
/ Liver - pathology
/ Liver cirrhosis
/ Liver diseases
/ Liver Diseases - etiology
/ Liver Diseases - metabolism
/ Liver Diseases - pathology
/ Male
/ Males
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ Nutrition
/ Oxidative Stress
/ Parenteral nutrition
/ Protein expression
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Sexes
/ Short bowel syndrome
/ Short Bowel Syndrome - complications
/ Short Bowel Syndrome - metabolism
/ Short Bowel Syndrome - pathology
/ Small intestine
/ Statistical analysis
/ Surgery
2025
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Liver injury in a preclinical model of short bowel syndrome is associated with impaired autophagy
Journal Article
Liver injury in a preclinical model of short bowel syndrome is associated with impaired autophagy
2025
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Overview
Critical for cellular maintenance and repair, autophagy recycles damaged or redundant cellular components. Dysregulated autophagy is associated with progressive cellular injury in various liver pathologies. However, the role of autophagy in intestinal failure-associated liver disease has not previously been investigated. Using a preclinical murine model of short bowel syndrome, we explored the role of autophagy impairment at early and late time points. Regardless of sex, small bowel resected (SBR) mice demonstrated significant liver injury compared to sham controls, exhibiting elevated serum transaminases, altered liver histology, and increased mRNA expression of endoplasmic reticulum stress marker (Ddit3) and oxidative stress marker (
Nqo1)
. Autophagy impairment was supported by increased p62 mRNA and protein expression in SBR liver and then confirmed with qualitative autophagy flux assay which suggested alteration of autophagy induction in SBR liver. Single nuclear RNA sequencing identified a cluster of hepatocytes in the SBR liver with increased p62 expression. These hepatocytes showed enrichment of genes related to the PI3K-Akt and ErbB pathways both which converge on mTORC1. Immunohistochemical distribution of pS6 confirmed increased mTORC1 activation in the SBR hepatocytes. Overall autophagy dysregulation is correlated with mTORC1 activation in SBR mice and is associated with greater liver injury.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
1-Phosphatidylinositol 3-kinase
/ Animals
/ Endoplasmic Reticulum Stress
/ Female
/ Females
/ Humanities and Social Sciences
/ Intestinal failure associated liver disease
/ Kinases
/ Liver
/ Male
/ Males
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Mice
/ Proteins
/ Science
/ Sexes
/ Short Bowel Syndrome - complications
/ Short Bowel Syndrome - metabolism
/ Short Bowel Syndrome - pathology
/ Surgery
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