| TRB3 is stimulated in diabetic kidneys, regulated by the ER stress marker CHOP, and is a suppressor of podocyte MCP-1. | |
| | |
MedLine Citation:
|
PMID: 20660016 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The prevalence of diabetic nephropathy continues to rise, highlighting the importance of investigating and discovering novel treatment strategies. TRB3 is a kinase-like molecule that modifies cellular survival and metabolism and interferes with signal transduction pathways. Herein, we report that TRB3 expression is increased in the kidneys of type 1 and type 2 diabetic mice. TRB3 is expressed in conditionally immortalized podocytes; however, it is not stimulated by elevated glucose. The diabetic milieu is associated with increased oxidative stress and circulating free fatty acids (FFA). We show that reactive oxygen species (ROS) such as H(2)O(2) and superoxide anion (via the xanthine/xanthine oxidase reaction) as well as the FFA palmitate augment TRB3 expression in podocytes. C/EBP homologous protein (CHOP) is a transcription factor that is associated with the endoplasmic reticulum stress response. CHOP expression increases in diabetic mouse kidneys and in podocytes treated with ROS and FFA. In podocytes, transfection of CHOP increases TRB3 expression, and ROS augment recruitment of CHOP to the proximal TRB3 promoter. MCP-1/CCL2 is a chemokine that contributes to the inflammatory injury associated with diabetic nephropathy. In these studies, we demonstrate that TRB3 can inhibit basal and stimulated podocyte production of MCP-1. In summary, enhanced ROS and/or FFA associated with the diabetic milieu induce podocyte CHOP and TRB3 expression. Because TRB3 inhibits MCP-1, manipulation of TRB3 expression could provide a novel therapeutic approach in diabetic kidney disease. |
| | |
Authors:
|
Elizabeth Morse; Jana Schroth; Young-Hyun You; Donald P Pizzo; Shinichi Okada; Satish Ramachandrarao; Volker Vallon; Kumar Sharma; Robyn Cunard |
Related Documents
:
|
446396 - Hypercalcemic effect of insulin in the chick. 3886416 - Muscular exercise in type i-diabetics. ii. hormonal and metabolic responses to moderate... 7476296 - Bromocriptine inhibits in vivo free fatty acid oxidation and hepatic glucose output in ... 7601726 - Dietary protein and(or) energy restriction in mares: plasma glucose, insulin, nonesteri... 16359826 - Alpha-thiolamines such as cysteine and cysteamine act as effective transglycating agent... 21156326 - Risk of progression of nephropathy in a population-based sample with type 2 diabetes. |
Publication Detail:
|
Type: Editorial; Research Support, N.I.H., Extramural Date: 2010-07-21 |
Journal Detail:
|
Title: American journal of physiology. Renal physiology Volume: 299 ISSN: 1522-1466 ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-04 Completed Date: 2010-12-02 Revised Date: 2011-11-01 |
Medline Journal Info:
|
Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: F965-72 Citation Subset: IM |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blotting, Western Cell Cycle Proteins / biosynthesis*, genetics, pharmacology Chemokine CCL2 / antagonists & inhibitors*, biosynthesis Chromatin / metabolism DNA / biosynthesis, genetics Diabetes Mellitus, Experimental / metabolism Diabetic Nephropathies / metabolism* Endoplasmic Reticulum / metabolism* Fluorescent Antibody Technique Immunoprecipitation Kidney / cytology, metabolism Male Mice Mice, Inbred C57BL Palmitates / metabolism Plasmids / genetics Podocytes / metabolism* RNA, Messenger / biosynthesis, genetics Reactive Oxygen Species / metabolism Reverse Transcriptase Polymerase Chain Reaction Transcription Factor CHOP / metabolism* Up-Regulation / drug effects |
| Grant Support | |
ID/Acronym/Agency:
|
P30-DK-063491/DK/NIDDK NIH HHS; R01-DK-56248/DK/NIDDK NIH HHS; U01-DK-076133-02/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Ccl2 protein, mouse; 0/Cell Cycle Proteins; 0/Chemokine CCL2; 0/Chromatin; 0/Palmitates; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/TRB3 protein, mouse; 147336-12-7/Transcription Factor CHOP; 9007-49-2/DNA |
| Comments/Corrections | |
Comment In:
|
Am J Physiol Renal Physiol. 2010 Nov;299(5):F963-4
[PMID:
20739396
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Genome-wide characterization of methylguanosine-capped and polyadenylated small RNAs in the rice bla...
Next Document: Renal autoregulation and passive pressure-flow relationships in diabetes and hypertension.