Dataset Information

A Novel Differentiated HuH-7 Cell Model to Examine Bile Acid Metabolism, Transport and Cholestatic Hepatotoxicity

ABSTRACT: Hepatic cell lines serve as economical and reproducible alternatives for primary human hepatocytes. However, the utility of hepatic cell lines to examine bile acid homeostasis and cholestatic toxicity is limited due to abnormal expression and function of bile acid-metabolizing enzymes, transporters, and the absence of canalicular formation. Previously, addition of dexamethasone (DEX) and Matrigel™ overlay restored expression, localization, and function of the bile salt export pump (BSEP), and formation of bile canalicular-like structures in four-week cultures of HuH-7 human hepatoma cells. We present here an improved differentiation process with the addition of 0.5% dimethyl sulfoxide (DMSO), which increased the expression and function of the major bile acid uptake and efflux transporters, sodium taurocholate co-transporting polypeptide (NTCP) and BSEP, respectively, in two-week HuH-7 cell cultures. This in vitro model was further characterized for expression of cytochrome P450 enzymes (CYP450s), uridine 5'-diphospho-glucuronosyltransferase (UGTs) and transporters using quantitative targeted proteomics.

INSTRUMENT(S): Q TRAP

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Chitra Saran

LAB HEAD: Kim Brouwer

PROVIDER: PXD031731 | Pride | 2022-10-14

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	HuH-7_Spls_21st_January_2021__CES___Various_.wiff	Wiff
	HuH-7_Spls_21st_January_2021__CES___Various_.wiff.scan	Wiff
	HuH-7_Spls_21st_January_2021__Transporters_.wiff	Wiff
	HuH-7_Spls_21st_January_2021__Transporters_.wiff.scan	Wiff
	HuH-7_Spls_21st_January_2021__UGTs.CYP450s_.wiff	Wiff

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A novel differentiated HuH-7 cell model to examine bile acid metabolism, transport and cholestatic hepatotoxicity.

Saran Chitra C Fu Dong D Ho Henry H Klein Abigail A Fallon John K JK Honkakoski Paavo P Brouwer Kim L R KLR

Scientific reports 20220822 1

Hepatic cell lines serve as economical and reproducible alternatives for primary human hepatocytes. However, the utility of hepatic cell lines to examine bile acid homeostasis and cholestatic toxicity is limited due to abnormal expression and function of bile acid-metabolizing enzymes, transporters, and the absence of canalicular formation. We discovered that culturing HuH-7 human hepatoma cells with dexamethasone (DEX) and 0.5% dimethyl sulfoxide (DMSO) for two weeks, with Matrigel overlay afte ...[more]

PMID: 35995956

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