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Cited by 320

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Conjugated Bile Acids Activate the Sphingosine–1–Phosphate Receptor 2 in Primary Rodent Hepatocytes

Open access
Studer, Elaine, Zhou, Xiqiao, Zhao, Renping, Wang, Yun, Takabe, Kazuaki, Nagahashi, Masayuki, Pandak, William M., Dent, Paul, Spiegel, Sarah, Shi, Ruihua, Xu, Weiren, Liu, Xuyuan, Bohdan, Pat, Zhang, Luyong, Zhou, Huiping, Hylemon, Phillip B.·2012·Hepatology
DOI 10.1002/hep.24681
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Abstract

Bile acids have been shown to be important regulatory molecules for cells in the liver and gastrointestinal tract. They can activate various cell signaling pathways including extracellular regulated kinase (ERK)1/2 and protein kinase B (AKT) as well as the G–protein–coupled receptor (GPCR) membrane–type bile acid receptor (TGR5/M–BAR). Activation of the ERK1/2 and AKT signaling pathways by conjugated bile acids has been reported to be sensitive to pertussis toxin (PTX) and dominant–negative Gαi in primary rodent hepatocytes. However, the GPCRs responsible for activation of these pathways have not been identified. Screening GPCRs in the lipid–activated phylogenetic family (expressed in HEK293 cells) identified sphingosine–1–phosphate receptor 2 (S1P2) as being activated by taurocholate (TCA). TCA, taurodeoxycholic acid (TDCA), tauroursodeoxycholic acid (TUDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), and S1P–induced activation of ERK1/2 and AKT were significantly inhibited by JTE–013, a S1P2 antagonist, in primary rat hepatocytes. JTE–013 significantly inhibited hepatic ERK1/2 and AKT activation as well as short heterodimeric partner (SHP) mRNA induction by TCA in the chronic bile fistula rat. Knockdown of the expression of S1P2 by a recombinant lentivirus encoding S1P2 shRNA markedly inhibited the activation of ERK1/2 and AKT by TCA and S1P in rat primary hepatocytes. Primary hepatocytes prepared from S1P2 knock out (S1P2 −/−) mice were significantly blunted in the activation of the ERK1/2 and AKT pathways by TCA. Structural modeling of the S1P receptors indicated that only S1P2 can accommodate TCA binding. In summary, all these data support the hypothesis that conjugated bile acids activate the ERK1/2 and AKT signaling pathways primarily through S1P2 in primary rodent hepatocytes. (Hepatology 2012)

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Metadata

Authors
Studer, E., Zhou, X., Zhao, R., Wang, Y., Takabe, K., Nagahashi, M., Pandak, W. M., Dent, P., Spiegel, S., Shi, R., Xu, W., Liu, X., Bohdan, P., Zhang, L., Zhou, H., & Hylemon, P. B.
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-01
Volume
55
Issue
1
Pages
267-276
ISSN
0270-9139 (ISSN-L)
DOI
10.1002/hep.24681
OpenAlex
W2144347270
Cited by
320
References
40
FWCI
3.53
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: Conjugated Bile Acids Activate the Sphingosine–1–Phosphate Receptor 2 in Primary Rodent Hepatocytes. https://app.cochat.ai/papers/10.1002/hep.24681
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Studer, E., Zhou, X., Zhao, R., Wang, Y., Takabe, K., Nagahashi, M., Pandak, W. M., Dent, P., Spiegel, S., Shi, R., Xu, W., Liu, X., Bohdan, P., Zhang, L., Zhou, H., & Hylemon, P. B. (2012). Conjugated Bile Acids Activate the Sphingosine–1–Phosphate Receptor 2 in Primary Rodent Hepatocytes. Hepatology. https://doi.org/10.1002/hep.24681

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