title: Hepatocyte proliferation in health and in liver failure.
abstract: Mammalian liver possesses an extraordinary capacity for compensatory growth in response to conditions that induce cell loss by physical, infectious, or toxic injury. In normal animals and humans, it is a tightly regulated process of both hypertrophy and hyperplasia involving different liver cell populations and a finely tuned interplay between growth factors, cytokines, extracellular matrix components and other regulators. The regeneration response is maximal when two-thirds of the liver is resected. When a lesser amount of parenchyma is removed, residual liver grows more slowly. Resections exceeding two-thirds of the liver mass also retard and diminish both DNA synthesis and mitotic activity and subtotal (90%) hepatectomy invariably results in the death of rats without regeneration. The underlying mechanisms of liver growth inhibition are poorly understood. In particular, only a few studies exist that provide insight into the mechanisms that control regeneration after extensive hepatocyte loss. In this regard, the role of growth-regulatory factors and other compounds that accumulate in the blood circulation as a result of hepatic insufficiency and liver cell death remains unclear. We have initiated studies of these mechanisms and demonstrated that in rats with low (10%) hepatocyte mass, a marked and sustained elevation of blood IL-6, HGF and TGF-b1 levels was associated with lack of hepatocyte proliferation and suppression of Stat3 DNA binding. While searching for the possible cause of inhibited IL-6/Stat3 signaling, we found that IL-6 receptor (IL-6R & gp130) was preserved, that nuclear Stat3 protein content was lowered, and that IL-6/Stat3 pathway inhibitors (SOCS-1, PIAS3) were induced during the pre-replicative Go-G1 period.
authors.affiliation: Liver Support Research Laboratory, Department of Surgery, Cedars-Sinai Medical Center and UCLA School of Medicine, 8700 Beverly Blvd., D-0418, Los Angeles, CA 90048, USA. Jacek.Rozga@cshs.org
authors.forename: Jacek
authors.initials: J
authors.lastname: Rozga
mesh_terms: D000818:Animals; D002455:Cell Division; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D017093:Liver Failure / Q000473:pathology*; D008115:Liver Regeneration