Novel systems biology insights using antifibrotic approaches for diabetic kidney disease

Handle URI:
http://hdl.handle.net/10754/575667
Title:
Novel systems biology insights using antifibrotic approaches for diabetic kidney disease
Authors:
RamachandraRao, Satish Posettihalli; Talwar, Priti; Ravasi, Timothy ( 0000-0002-9950-465X ) ; Sharma, Kumar
Abstract:
Although several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. To explore the therapeutic potential of PFD, we studied the PFD-treated db/db diabetic mouse kidney by liquid chromatography-tandem mass spectrometry proteomics. A total of 21 proteins unique to PFD-treated diabetic kidneys were identified. Analysis of gene ontology and protein-protein interactions of these proteins suggested that PFD may regulate RNA translation. Two key proteins involved in mRNA translation initiation and elongation were further evaluated and found to be regulated by PFD at the level of phosphorylation. In conclusion, insights from combining proteomics and bioinformatics improve the likelihood of rapid advancement of novel clinical therapies focused on reducing inflammation and fibrosis for diabetic complications. © 2010 Expert Reviews Ltd.
KAUST Department:
Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Integrative Systems Biology Lab
Publisher:
Informa Healthcare
Journal:
Expert Review of Endocrinology & Metabolism
Issue Date:
Jan-2010
DOI:
10.1586/eem.09.72
Type:
Article
ISSN:
17446651
Appears in Collections:
Articles; Bioscience Program; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorRamachandraRao, Satish Posettihallien
dc.contributor.authorTalwar, Pritien
dc.contributor.authorRavasi, Timothyen
dc.contributor.authorSharma, Kumaren
dc.date.accessioned2015-08-24T08:35:25Zen
dc.date.available2015-08-24T08:35:25Zen
dc.date.issued2010-01en
dc.identifier.issn17446651en
dc.identifier.doi10.1586/eem.09.72en
dc.identifier.urihttp://hdl.handle.net/10754/575667en
dc.description.abstractAlthough several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. To explore the therapeutic potential of PFD, we studied the PFD-treated db/db diabetic mouse kidney by liquid chromatography-tandem mass spectrometry proteomics. A total of 21 proteins unique to PFD-treated diabetic kidneys were identified. Analysis of gene ontology and protein-protein interactions of these proteins suggested that PFD may regulate RNA translation. Two key proteins involved in mRNA translation initiation and elongation were further evaluated and found to be regulated by PFD at the level of phosphorylation. In conclusion, insights from combining proteomics and bioinformatics improve the likelihood of rapid advancement of novel clinical therapies focused on reducing inflammation and fibrosis for diabetic complications. © 2010 Expert Reviews Ltd.en
dc.publisherInforma Healthcareen
dc.subjectEEF2en
dc.subjectEIF4Een
dc.subjectKidney biopsy proteomicsen
dc.subjectKidney proteomicsen
dc.subjectMRNA processingen
dc.subjectMRNA translationen
dc.subjectPhosphataseen
dc.subjectPirfenidoneen
dc.subjectProtein phosphorylationen
dc.titleNovel systems biology insights using antifibrotic approaches for diabetic kidney diseaseen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentBioscience Programen
dc.contributor.departmentIntegrative Systems Biology Laben
dc.identifier.journalExpert Review of Endocrinology & Metabolismen
dc.contributor.institutionVeterans Administration San Diego Healthcare System, La Jolla, CA, United Statesen
dc.contributor.institutionDepartment of Medicine, Center for Renal Translational Medicine, University of California, San Diego, San Diego, CA 92093, United Statesen
dc.contributor.institutionDepartment of Bioengineering, Jacobs School of Engineering, University of California, San Diego, CA, United Statesen
dc.contributor.institutionScripps NeuroAIDS Preclinical Studies Centre, 9500 Gilman Drive, La Jolla, CA 92093, United Statesen
dc.contributor.institutionCenter for Renal Translational Medicine, UCSD/VA San Diego Health System, La Jolla, CA 92093-0711, United Statesen
kaust.authorRavasi, Timothyen
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