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22 February 2002

Hepatocyte proliferation in health and in liver failure.

Jacek Rozga

Med Sci Monit 2002; 8(2): RA32-38 :: ID: 420920

Abstract

Mammalian liver possesses an extraordinary capacity for compensatory growthin response to conditions that induce cell loss by physical, infectious, or toxic injury. In normal animalsand humans, it is a tightly regulated process of both hypertrophy and hyperplasia involving differentliver cell populations and a finely tuned interplay between growth factors, cytokines, extracellularmatrix components and other regulators. The regeneration response is maximal when two-thirds of the liveris resected. When a lesser amount of parenchyma is removed, residual liver grows more slowly. Resectionsexceeding two-thirds of the liver mass also retard and diminish both DNA synthesis and mitotic activityand subtotal (90%) hepatectomy invariably results in the death of rats without regeneration. The underlyingmechanisms of liver growth inhibition are poorly understood. In particular, only a few studies existthat provide insight into the mechanisms that control regeneration after extensive hepatocyte loss. Inthis regard, the role of growth-regulatory factors and other compounds that accumulate in the blood circulationas a result of hepatic insufficiency and liver cell death remains unclear. We have initiated studiesof these mechanisms and demonstrated that in rats with low (10%) hepatocyte mass, a marked and sustainedelevation of blood IL-6, HGF and TGF-b1 levels was associated with lack of hepatocyte proliferation andsuppression 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-G1period.

Keywords: Cell Division, Hepatocytes, Liver, Liver failure, Liver Regeneration

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750