Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Denk, H; Abuja, PM; Zatloukal, K.
Mallory-Denk bodies and hepatocellular senescence: a causal relationship?
Virchows Arch. 2024;
Doi: 10.1007/s00428-024-03748-1
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- Führende Autor*innen der Med Uni Graz
- Denk Helmut
- Co-Autor*innen der Med Uni Graz
- Abuja Peter Michael
- Zatloukal Kurt
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- Abstract:
- Mallory-Denk bodies (MDBs) are hepatocellular cytoplasmic inclusions, which occur in certain chronic liver diseases, such as alcohol-related (ASH) and metabolic dysfunction-associated (MASH) steatohepatitis, copper toxicosis, some drug-induced liver disorders, chronic cholangiopathies, and liver tumors. Our study focused on the expression of the senescence markers p21WAF1/cip1 and p16INK4a in hepatocytes containing MDBs in steatohepatitis, chronic cholangiopathies with fibrosis or cirrhosis, Wilson's disease, and hepatocellular carcinomas. Cytoplasm and nuclei of MDB-containing hepatocytes as well as MDB inclusions, except those associated with carcinoma cells, were strongly p16-positive, p21-positive, as well as p21-negative nuclei in MDB-containing hepatocytes which were observed whereas MDBs were p21-negative. Expression of the senescence marker p16 suggests that MDB formation reflects an adaptive response to chronic stress resembling senescence with its consequences, i.e., expression of inflammation- and fibrosis-prone secretome. Thus, senescence can be regarded as "double-edged sword" since, on the one hand, it may be an attempt of cellular defense, but, on the other, also causes further and sustained damage by inducing inflammation and fibrosis related to the senescence-associated secretory phenotype and thus progression of chronic liver disease.
- Find related publications in this database (Keywords)
- Steatohepatitis
- Chronic cholangiopathy
- Keratins
- Mallory-Denk bodies
- Cellular senescence