NDLI: Overexpression of G-Protein-Coupled Receptor 40 Enhances the Mitogenic Response to Epoxyeicosatrienoic Acids

Content Provider	PubMed Central
Author	Ma, Seong Kwon Wang, Yinqiu Chen, Jianchun Zhang, Ming-zhi Harris, Raymond C. Chen, Jian-kang
Editor	Sands, Jeff M.
Copyright Year	2015
Abstract	The cytochrome P450 epoxygenase-dependent arachidonic acid metabolites, epoxyeicosatrienoic acids (EETs), are potent survival factors and mitogens for renal epithelial cells, but the molecular identity in the cells that initiates the mitogenic signaling of EETs has remained elusive. We screened kidney cell lines for the expression of G-protein-coupled receptor 40 (GPR40) and found that the porcine renal tubular epithelial cell line LLCPKcl4, which has been previously demonstrated to be sensitive to the mitogenic effect of EETs, expresses higher levels of GPR40 mRNA and protein than the human embryonic kidney cell line HEK293. EETs induced only a weak mitogenic EGFR signaling and mild cell proliferation in HEK293 cells. To determine whether GPR40 expression level is what mediates the mitogenic sensitivity of cells to EETs, we created a human GPR40 (hGPR40) cDNA construct and transfected it into HEK293 cells and picked up a number of stable transfectants. We found that GPR40 overexpression in HEK293 cells indeed significantly enhanced EET-induced cell proliferation and markedly augmented EGFR phosphorylation ERK activation, which were inhibited by the EGFR tyrosine kinase inhibitor, AG1478, or the HB-EGF inhibitor, CRM197. EETs significantly enhanced release of soluble HB-EGF, a natural ligand of EGFR, into the culture medium of hGPR40-transfected HEK293 cells, compared to empty vector-transfected cells. In mouse kidneys, markedly higher level of GPR40 protein was found in the cortex and outer stripe of outer medulla compared to the inner stripe of outer medulla and inner medulla. In situ hybridization confirmed that GPR40 mRNA was localized to a subset of renal tubules in the kidney, including the cortical collecting duct. Thus, this study provides the first demonstration that upregulation of GPR40 expression enhances the mitogenic response to EETs and a relatively high expression level of GPR40 is detected in a subset of tubules including cortical collecting ducts in the mammalian kidney.
Related Links	http://dx.doi.org/10.1371/journal.pone.0113130
Starting Page	113130
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	2
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-02-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

The Viral G Protein-Coupled Receptor ORF74 Hijacks β-Arrestins for Endocytic Trafficking in Response to Human Chemokines

The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake

The Origin and Evolution of G Protein-Coupled Receptor Kinases

Involvement of the G-Protein-Coupled Dopamine/Ecdysteroid Receptor DopEcR in the Behavioral Response to Sex Pheromone in an Insect

G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells

A Ligand Channel through the G Protein Coupled Receptor Opsin

Production of a Bioengineered G-Protein Coupled Receptor of Human Formyl Peptide Receptor 3

G-Protein Coupled Receptor 30 (GPR30): A Novel Regulator of Endothelial Inflammation

Regulation of C3a Receptor Signaling in Human Mast Cells by G Protein Coupled Receptor Kinases

Overexpression of G-Protein-Coupled Receptor 40 Enhances the Mitogenic Response to Epoxyeicosatrienoic Acids

Similar Documents

The Viral G Protein-Coupled Receptor ORF74 Hijacks β-Arrestins for Endocytic Trafficking in Response to Human Chemokines

The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake

The Origin and Evolution of G Protein-Coupled Receptor Kinases

Involvement of the G-Protein-Coupled Dopamine/Ecdysteroid Receptor DopEcR in the Behavioral Response to Sex Pheromone in an Insect

G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells

A Ligand Channel through the G Protein Coupled Receptor Opsin

Production of a Bioengineered G-Protein Coupled Receptor of Human Formyl Peptide Receptor 3

G-Protein Coupled Receptor 30 (GPR30): A Novel Regulator of Endothelial Inflammation

Regulation of C3a Receptor Signaling in Human Mast Cells by G Protein Coupled Receptor Kinases

Overexpression of G-Protein-Coupled Receptor 40 Enhances the Mitogenic Response to Epoxyeicosatrienoic Acids