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Platelet C-Type Lectin-Like Receptor 2 Reduces Cholestatic Liver Injury in Mice
- Source :
- The American journal of pathology. 190(9)
- Publication Year :
- 2019
-
Abstract
- Cholestatic liver injury leads to liver dysfunction. The available evidence suggests that platelets can either promote or reduce liver injury and fibrosis. This study focused on the functions of the C-type lectin-like receptor 2 (CLEC-2), a new special platelet receptor that binds with podoplanin-activating platelets. The role of CLEC-2 and podoplanin in cholestatic liver injury was investigated. Mice were injected intraperitoneally with weekly doses of anti-CLEC-2 antibody (2A2B10) to achieve effective CLEC-2 inhibition in their platelets. Next, left and middle hepatic bile duct ligation (BDL) procedures were performed, and mice were euthanized 1 week later (2A2B10-BDL group). In addition, mice were prepared for control groups, and relevant histological and laboratory variables were compared among these groups. The inhibition of CLEC-2 resulted in increasing hepatocellular necrosis, hepatic inflammation, and liver fibrosis. In addition, podoplanin was strongly expressed in hepatic sinusoidal endothelial cells in BDL-treated mice. Moreover, in 2A2B10-BDL mice, total plasma bile acid levels were significantly increased. In summary, podoplanin is expressed on hepatic sinusoidal endothelial cells upon BDL. Platelets bind with podoplanin via CLEC-2 and become activated. As a result, the total bile acid pool is decreased. Therefore, the CLEC-2-podoplanin interaction promotes liver protection and inhibits liver fibrosis after cholestatic liver injury.
- Subjects :
- Blood Platelets
Male
medicine.medical_specialty
medicine.drug_class
030204 cardiovascular system & hematology
Pathology and Forensic Medicine
03 medical and health sciences
Mice
0302 clinical medicine
C-type lectin
Fibrosis
Internal medicine
medicine
Animals
Platelet
Lectins, C-Type
Receptor
Liver injury
Cholestasis
Membrane Glycoproteins
Bile acid
biology
business.industry
Endothelial Cells
medicine.disease
Platelet Activation
Mice, Inbred C57BL
Endocrinology
Podoplanin
biology.protein
030211 gastroenterology & hepatology
Antibody
business
Subjects
Details
- ISSN :
- 15252191
- Volume :
- 190
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- The American journal of pathology
- Accession number :
- edsair.doi.dedup.....b656ea0c118a3aae772418c696f7e299