Increased bile lithogenicity by SCP2 via HMGCR and CYP7A1 regulation in human hepatocytes.
OBJECTIVE
Lithogenic bile is a major cause of cholesterol gallstones, and hypersecretion of biliary cholesterol is believed to be an important cause of lithogenic bile. Sterol carrier protein 2 plays a key role in cholesterol trafficking and may regulate lipid metabolism in hepatocytes.


METHODS
Human sterol carrier protein 2 cDNA was cloned and shRNAs against sterol carrier protein 2 were synthesized. Sterol carrier protein 2-modified hepatocyte models were then set up using adenoviral vectors to study its regulatory function in lipid metabolism. Following overexpression and knockdown of sterol carrier protein 2, HMGCR and CYP7A1 expression as well as the secretion of bile lipids were studied in hepatocytes.


RESULTS
The expression of HMGCR was enhanced by sterol carrier protein 2 overexpression and downregulated by sterol carrier protein 2 knockdown. The concentration of cholesterol in the supernatant was elevated under sterol carrier protein 2 overexpression and decreased under sterol carrier protein 2 downregulation. Although sterol carrier protein 2 overexpression could repress the expression of CYP7A1, no changes were noted in total bile acid concentration. Thus, the expression of sterol carrier protein 2 could influence bile lithogenicity in the sterol carrier protein 2-modified hepatocyte models.


CONCLUSIONS
Sterol carrier protein 2 may function as a moderator of HMGCR in human hepatocytes. Likely influences cholesterol metabolism and bile lithogenicity of human liver cells by regulating the expression of HMGCR and CYP7A1.
Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Department of Surgery, Tianjin, China.
Cui
C
Yunfeng
Li
L
Zhonglian
Zhao
Z
Erpeng
Zhang
Z
Ju
Cui
C
Naiqiang
D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D034741:RNA, Small Interfering; D014162:Transfection; D015854:Up-Regulation
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D034741:RNA, Small Interfering; C072087:sterol carrier proteins; D002784:Cholesterol; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; C553219:CYP7A1 protein, human; D002790:Cholesterol 7-alpha-Hydroxylase