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Extracellular matrix regulates the hepatocellular heat shock response.
J E Gosnell1, C B Wong, Z L Kumwenda
1UCSF Surgical Research Laboratory at San Francisco General Hospital, San Francisco, California 94110, USA.
The Journal of Surgical Research
|May 19, 2000
Summary
The liver extracellular matrix (ECM) significantly impacts hepatocyte function. Collagen-rich ECM in cirrhosis may drive hepatocellular dysfunction, affecting viability and cytokine response, but not TNF-alpha-induced apoptosis.
Area of Science:
- Hepatology and extracellular matrix biology.
Background:
- Cirrhosis involves liver collagen accumulation and hepatocellular dysfunction.
- Extracellular matrix (ECM) can modulate cellular functions.
- This study investigated the ECM's role in hepatocellular dysfunction.
Purpose of the Study:
- To examine how different ECM environments affect hepatocyte behavior.
- To compare hepatocyte viability, cytokine response, and heat shock response in varied ECMs.
- To assess ECM influence on thermotolerance and protection against apoptosis.
Main Methods:
- Primary rat hepatocytes cultured on collagen (monolayer) or in laminin-rich ECM (spheroids).
- Assessed hepatocyte viability, nitric oxide production, heat shock protein 70 (hsp72) expression, and thermotolerance.
- Evaluated protection against tumor necrosis factor (TNF)-alpha/actinomycin-D-induced apoptosis after heat shock.
Main Results:
- Hepatocytes on collagen showed reduced viability and spontaneous apoptosis.
- Spheroid hepatocytes had better viability and nitric oxide production.
- Hepatocyte spheroids, but not monolayers, developed thermotolerance; hsp72 was induced in both.
Conclusions:
- The ECM composition critically influences hepatocellular viability, cytokine response, and thermotolerance.
- Progressive collagen deposition in cirrhosis may contribute to hepatocellular dysfunction.
- TNF-alpha-induced apoptosis was independent of the ECM environment in this study.