Metallothionein Expression in Horses With Chronic Liver Disease and Its Correlation With Ki-67 Immunoreactivity.
Abstract: Chronic liver disease is an important cause of illness in horses, and treatment is mainly supportive. Research into new treatment modalities for humans has shown promising data regarding metallothionein (MT), which has been shown to possess regenerative, antifibrotic, and anti-inflammatory properties. This study aimed to examine the relationship between hepatic MT expression and the histopathologic markers of hepatic inflammation, fibrosis and bile duct proliferation, as well as cellular regeneration in 77 selected cases of chronic liver disease in horses. We hypothesized that higher MT expression would be associated with increased heptocellular proliferation and decreased fibrosis, inflammation, and bile duct proliferation. Hepatocellular MT expression was evaluated with immunohistochemistry. Additionally, cellular regeneration was evaluated with immunohistochemistry for Ki-67, a protein expressed during all active stages of the cell cycle. The severity of inflammation and fibrosis was scored, and bile duct proliferation was assessed by counting bile duct profiles. MT expression was observed in 73 of 77 (94.8%) cases of chronically diseased livers. Ki-67 expression was seen in resident Kupffer cells ( n = 42, 54.6%), lymphocytes ( n = 39, 50.7%), bile duct epithelium ( n = 10, 13.0%), and hepatocytes ( n = 8, 10.4%). MT expression was significantly associated with Ki-67 staining in bile duct epithelium and Kupffer cells. Additionally, median MT expression was higher in cases containing lymphocytic infiltrates as compared with cases with no lymphocytic infiltrate ( P < .05). These findings are the first known report of MT expression within chronic equine hepatic disease.
Publication Date: 2018-06-04 PubMed ID: 29865992DOI: 10.1177/0300985818777802Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper examines the correlation between metallothionein (MT) expression and features of chronic liver disease in horses, suggesting potential future treatment avenues.
Research Overview
The research focusses on potential treatment paths for chronic liver disease in horses and examines the role of a protein called metallothionein (MT). This protein is known to possess regenerative, anti-inflammatory, and antifibrotic properties. The researchers investigated the relationship between MT expression and the presence of indicators of liver disease such as inflammation, fibrosis, bile duct proliferation, and cellular regeneration in 77 cases of chronic liver disease in horses.
Hypothesis and Evaluation Methods
- This study was based on the hypothesis that a higher expression of MT correlates with an increase in hepatocellular proliferation and a decrease in fibrosis, inflammation, and bile duct proliferation.
- The research team evaluated the MT expression in the liver cells of the affected horses through immunohistochemistry, a technique employed in the detection of specific proteins in cells of a tissue section.
- Moreover, they measured the level of cellular regeneration through immunohistochemistry for Ki-67, a protein that is expressed during all active stages of the cell cycle.
- The severity of inflammation and fibrosis was scored, and bile duct proliferation was assessed by counting bile duct profiles.
Findings and Conclusions
- MT expression was observed in almost 95% of the examined cases of chronically diseased horse livers.
- In addition to hepatocytes, Ki-67 expression was observed in Kupffer cells, lymphocytes, and bile duct epithelium.
- The study found a significant association between MT expression and Ki-67 staining in bile duct epithelium and Kupffer cells.
- A higher median MT expression was found in cases containing lymphocytic infiltrates as compared with cases without a lymphocytic infiltrate.
- This first-ever report of MT expression within chronic equine hepatic disease provides new insights and potential therapeutic directions for chronic liver disease in horses.
Cite This Article
APA
Verhoef JNC, Allen AL, Harding JCS, Al-Dissi AN.
(2018).
Metallothionein Expression in Horses With Chronic Liver Disease and Its Correlation With Ki-67 Immunoreactivity.
Vet Pathol, 55(5), 703-710.
https://doi.org/10.1177/0300985818777802 Publication
Researcher Affiliations
- 1 Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
- 1 Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
- 2 Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
- 1 Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
MeSH Terms
- Animals
- Bile Ducts / metabolism
- Bile Ducts / pathology
- End Stage Liver Disease / metabolism
- End Stage Liver Disease / pathology
- End Stage Liver Disease / veterinary
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Ki-67 Antigen / metabolism
- Kupffer Cells / metabolism
- Kupffer Cells / pathology
- Liver / metabolism
- Liver / pathology
- Lymphocytes / metabolism
- Lymphocytes / pathology
- Metallothionein / metabolism
Citations
This article has been cited 4 times.- Mohammed O, Tufa A, Gizaw ST. Emerging Roles of Metallothioneins in Human Pathophysiology: A Review. Health Sci Rep 2025 Sep;8(9):e71279.
- Tangphokhanon W, Pradidarcheep W, Lametschwandtner A. α-mangostin preserves hepatic microvascular architecture in fibrotic rats as shown by scanning electron microscopy of vascular corrosion casts. Biomed Rep 2021 Jun;14(6):48.
- Jose D, Allen AL, Blakley B, Al-Dissi A. Evaluation of metallothionein and Ki-67 expression in chronic cholangiohepatitis in cats. Can J Vet Res 2021 Jan;85(1):36-44.
- Tomlinson JE, Jager M, Struzyna A, Laverack M, Fortier LA, Dubovi E, Foil LD, Burbelo PD, Divers TJ, Van de Walle GR. Tropism, pathology, and transmission of equine parvovirus-hepatitis. Emerg Microbes Infect 2020;9(1):651-663.
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