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Loss of integrin linked kinase from mouse hepatocytesin vitro andin vivo results in apoptosis and hepatitis
- Source :
- Hepatology. 45:1025-1034
- Publication Year :
- 2007
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2007.
-
Abstract
- Extracellular matrix (ECM) is fundamental for the survival of cells within a tissue. Loss of contact with the surrounding ECM often causes altered cell differentiation or cell death. Hepatocytes cultured without matrix lose patterns of hepatocyte-specific gene expression and characteristic cellular micro-architecture. However, differentiation is restored after the addition of hydrated matrix preparations to dedifferentiated hepatocytes. Integrin-linked kinase (ILK) is an important component of cell–ECM adhesions transmitting integrin signaling to the interior of the cell. ILK has been implicated in many fundamental cellular processes such as differentiation, proliferation, and survival. In this study, we investigated the role of ILK in mouse hepatocytes in vitro as well as in vivo. Depletion of ILK from primary mouse hepatocytes resulted in enhanced apoptosis. This was accompanied by increased caspase 3 activity and a significant decrease in expression of PINCH and α-parvin, which, along with ILK, form a stable well-characterized ternary complex at cell–ECM adhesions. The induction of apoptosis caused by ILK depletion could be substantially reversed by simultaneous overexpression of ILK, indicating that apoptosis is indeed a consequence of ILK removal. These results were further corroborated via in vivo data showing that adenoviral delivery of Cre-recombinase in ILK-floxed animals by tail vein injection resulted in acute hepatitis, with a variety of pathological findings including inflammation, fatty change, and apoptosis, abnormal mitoses, hydropic degeneration, and necrosis. Conclusion: Our results demonstrate the importance of ILK and integrin signaling for the survival of hepatocytes and the maintenance of normal liver function. (HEPATOLOGY 2007.)
- Subjects :
- Programmed cell death
Pathology
medicine.medical_specialty
Cellular differentiation
Integrin
Gene Expression
Apoptosis
Protein Serine-Threonine Kinases
Biology
Transfection
Adenoviridae
Hepatitis
Hydropic degeneration
Extracellular matrix
Mice
medicine
Animals
Integrin-linked kinase
Phosphorylation
Cells, Cultured
Adaptor Proteins, Signal Transducing
Mice, Knockout
Integrases
Hepatology
Kinase
Integrin beta1
Microfilament Proteins
Membrane Proteins
LIM Domain Proteins
medicine.disease
Extracellular Matrix
Cell biology
DNA-Binding Proteins
Liver
embryonic structures
Hepatocytes
biology.protein
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 15273350 and 02709139
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Hepatology
- Accession number :
- edsair.doi.dedup.....678854dea50f787dd841e23c61b1f77c