TY - JOUR
T1 - Novel systems biology insights using antifibrotic approaches for diabetic kidney disease
AU - RamachandraRao, Satish Posettihalli
AU - Talwar, Priti
AU - Ravasi, Timothy
AU - Sharma, Kumar
N1 - KAUST Repository Item: Exported on 2020-10-01
PY - 2014/1/10
Y1 - 2014/1/10
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/575667
UR - http://www.tandfonline.com/doi/full/10.1586/eem.09.72
UR - http://www.scopus.com/inward/record.url?scp=77949780004&partnerID=8YFLogxK
U2 - 10.1586/eem.09.72
DO - 10.1586/eem.09.72
M3 - Article
C2 - 30934387
SN - 1744-6651
VL - 5
SP - 127
EP - 135
JO - Expert Review of Endocrinology & Metabolism
JF - Expert Review of Endocrinology & Metabolism
IS - 1
ER -
