Enhanced apoptosis characterizes several pathologies affecting human liver. This study sought to determine whether apoptosis is involved in the formation of fibrotic lesions occurring in hepatic disease. The expression of Bcl-2 was analysed, and of 'tissue' transglutaminase (tTG), a cross-linking enzyme which recent evidence suggests plays a role in the formation of fibrotic lesions in experimental settings. Regardless of the degree of liver injury, tTG abnormally accumulated in the liver cells adjacent to fibrotic tissue. Many cells showing DNA fragmentation and morphological features of apoptosis were also observed near fibrotic lesions. Bcl-2 was detected predominantly in infiltrating lymphocytes within the liver tissue. Marked staining for both tTG protein and chromatin was also observed in the acellular fibrotic tissue, which suggested an active release of intracellular macromolecules from the dying cells into the extracellular matrix. This study indicates that fibrogenesis in the liver is associated with the release of tTG from dying cells. By cross-linking extracellular matrix proteins, this enzyme might play a role in the formation of fibrotic lesions.

'Tissue' transglutaminase release from apoptotic cells into extracellular matrix during human liver fibrogenesis

Hassan, Cesare;
1999-01-01

Abstract

Enhanced apoptosis characterizes several pathologies affecting human liver. This study sought to determine whether apoptosis is involved in the formation of fibrotic lesions occurring in hepatic disease. The expression of Bcl-2 was analysed, and of 'tissue' transglutaminase (tTG), a cross-linking enzyme which recent evidence suggests plays a role in the formation of fibrotic lesions in experimental settings. Regardless of the degree of liver injury, tTG abnormally accumulated in the liver cells adjacent to fibrotic tissue. Many cells showing DNA fragmentation and morphological features of apoptosis were also observed near fibrotic lesions. Bcl-2 was detected predominantly in infiltrating lymphocytes within the liver tissue. Marked staining for both tTG protein and chromatin was also observed in the acellular fibrotic tissue, which suggested an active release of intracellular macromolecules from the dying cells into the extracellular matrix. This study indicates that fibrogenesis in the liver is associated with the release of tTG from dying cells. By cross-linking extracellular matrix proteins, this enzyme might play a role in the formation of fibrotic lesions.
1999
Adult
Apoptosis
Budd-Chiari Syndrome
DNA Fragmentation
Extracellular Matrix
Female
Hepatitis
Hepatitis B
Chronic
Hepatitis
Alcoholic
Hepatitis
Chronic
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Liver
Male
Middle Aged
Transglutaminases
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/75693
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