Oncotarget

Research Papers:

The G-protein-coupled bile acid receptor Gpbar1 (TGR5) protects against renal inflammation and renal cancer cell proliferation and migration through antagonizing NF-κB and STAT3 signaling pathways

Jia Su, Qiqi Zhang, Hui Qi, Linlin Wu, Yuanqiang Li, Donna Yu, Wendong Huang, Wei-Dong Chen and Yan-Dong Wang _

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Oncotarget. 2017; 8:54378-54387. https://doi.org/10.18632/oncotarget.17533

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Abstract

Jia Su1,*, Qiqi Zhang1,*, Hui Qi2,*, Linlin Wu1, Yuanqiang Li1, Donna Yu4, Wendong Huang4, Wei-Dong Chen2,3 and Yan-Dong Wang1

1State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P.R. China

2Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, Henan, P.R. China

3Key Laboratory of Molecular Pathology, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot, Inner Mongolia, P.R. China

4Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA

*These authors contributed equally to this work

Correspondence to:

Yan-Dong Wang, email: [email protected]

Wei-Dong Chen, email: [email protected]

Keywords: Gpbar1, TGR5, renal inflammation, STAT3, NF-κB

Received: July 04, 2016     Accepted: April 12, 2017     Published: April 29, 2017

ABSTRACT

Gpbar1 (TGR5), a G-protein-coupled bile acid membrane receptor, is well known for its roles in regulation of glucose metabolism and energy homeostasis. In the current work, we found that TGR5 activation by its ligand suppressed lipopolysaccharide (LPS)-induced proinflammatory gene expression in wild-type (WT) but not TGR5−/− mouse kidney. Furthermore, we found that TGR5 is a suppressor of kidney cancer cell proliferation and migration. We show that TGR5 activation antagonized NF-κB and STAT3 signaling pathways through suppressing the phosphorylation of IκBα, the translocation of p65 and the phosphorylation of STAT3. TGR5 overexpression with ligand treatment inhibited gene expression mediated by NF-κB and STAT3. These results suggest that TGR5 antagonizes kidney inflammation and kidney cancer cell proliferation and migration at least in part by inhibiting NF-κB and STAT3 signaling. These findings identify TGR5 may serve as an attractive therapeutic tool for human renal inflammation related diseases and cancer.


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