Expression of the hepatic Niemann-Pick C1 like 1 protein gene is sensitive to rosuvastatin treatment of primary human hepatocytes.
Statins act by reducing hepatic cholesterol synthesis, thus stimulating uptake of serum cholesterol. Statin therapy modulates a number of genes involved in hepatic cholesterol homeostasis. These have rarely been analyzed simultaneously in the same experimental setting, with virtually no studies of primary human hepatocytes. This study analyzed the efficacy of rosuvastatin in the coordinated regulation of a number of genes implicated in cholesterol metabolism in primary human hepatocytes. Expression of five cholesterol-related genes were significantly upregulated, notably the Niemann-Pick C1 like 1 protein, for whom functional studies have been essentially limited to the intestine. Two genes were significantly downregulated, including sterol recognition element binding protein-1 gene that is implicated in control of hepatic lipogenesis. The results show the coordinated regulation of several genes implicated in hepatic cholesterol homeostasis and suggest therapeutic targets that could complement that clinical action of statins.
Brulhart-Meynet
Marie-Claude
MC
Department of Internal Medicine, Cantonal Hospital, Geneva, Switzerland.
Deakin
Sara P
SP
Sgroi
Antonino
A
Buhler
Leo
L
James
Richard William
RW
D002478:Cells, Cultured; D005464:Fluorobenzenes / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
D005464:Fluorobenzenes; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium