Early induction of LDL receptor gene during rat liver regeneration

Abstract

After partial hepatectomy in the rat, there is substantial lipid accumulation in the liver. No information is available on the possible role of receptor-mediated endocytosis in this process. Since the low density lipoprotein (LDL) receptor is stimulated as a part of an early growth response in cell culture (Ellsworth et al.: Biochem. J. 279:175-187, 1991), the metabolism of this receptor during liver regeneration was studied. The mRNA and membrane protein level of the receptor were measured in the liver and in the adrenal glands at different times after partial hepatectomy, corresponding to different phases of the cell cycle. A discontinuous pattern of receptor expression is detectable in the regenerating liver; a large increase of mRNA and membrane protein occurs at an early time (2-4 h), suggesting that there is induction of LDL receptor gene transcription shortly after partial hepatectomy. This response seems specific for the liver following injury since the adrenal receptor does not show a different pattern in partially hepatectomized rats and sham-operated controls. After returning to control levels, the LDL receptor again increases slightly above control at 24 h, a time when cell replication begins.

Impaired liver regeneration in Ldlr−/− mice is associated with an altered hepatic profile of cytokines, growth factors, and lipids

“…For instance, the hypolipidemia observed in serum samples from partial hepatectomized rats correlates with the increase in hepatic triglyceride content and supports the idea that lipid transport is affected [18]. In addition, the Ldlr has been shown to be overexpressed in liver after PH [19]. Furthermore, the expression of the Ldlr gene is induced as a part of an early growth response in Hep-G2 cells [20].…”

Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation

“…36 In vitro, HCV internal ribosome entry site activity and replication were found to be higher in actively dividing cells, and it is possible that viral translation may be enhanced by factors that stimulate the regeneration of hepatocytes. 37,38 Moreover, there are experimental data suggesting that liver regeneration induces LDL receptor expression, 39 which might facilitate HCV entrance into the hepatocytes. 40 The absence of significant differences in viral load between LDLT and CLT at the analyzed time points does not exclude increased viral production in regenerating cells, as viral load also depends on the number of cells producing viral particles and on viral clearance mechanisms.…”

Role of adult living donor liver transplantation in patients with hepatitis C

“…One mechanism of cell entry of HCV is endocytosis through the LDL receptor, 17,18 in which expression is increased four-to fivefold in replicating hepatocytes. 19,20 Therefore, proliferating hepatocytes may increase cell entry of HCV through enhanced production of the LDL receptor. Table 2 lists clinical and molecular factors that could impact both positively and negatively on recurrent HCV in living donor liver transplant recipients.…”