Novel systems biology insights using antifibrotic approaches for diabetic kidney disease

Satish P RamachandraRao; Priti Talwar; Timothy Ravasi; Kumar Sharma

doi:10.1586/eem.09.72

Novel systems biology insights using antifibrotic approaches for diabetic kidney disease

Expert Rev Endocrinol Metab. 2010 Jan;5(1):127-135. doi: 10.1586/eem.09.72.

Authors

Satish P RamachandraRao¹, Priti Talwar², Timothy Ravasi³, Kumar Sharma⁴

Affiliations

¹ a Veterans Administration San Diego Healthcare System, La Jolla, CA, USA and Center for Renal Translational Medicine, Division of Nephrology and Hypertension, Department of Medicine, 407 Stein Clinical Research Building, Mail Box #0711, University of California, San Diego, La Jolla, CA 92093, USA. satishrao@ucsd.edu.
² b Center for Renal Translational Medicine, Division of Nephrology and Hypertension, Department of Medicine, 407 Stein Clinical Research Building, Mail Box #0711, University of California, San Diego, La Jolla, CA 92093, USA and Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, CA, USA. ptalwar@ucsd.edu.
³ c Division of Life Sciences and Engineering, Computational Bioscience Research Center (CBRC), King Abdullah University for Science and Technology (KAUST), Jeddah, Saudi Arabia and Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, CA, USA and The Scripps NeuroAIDS Preclinical Studies Centre, 9500 Gilman Drive, La Jolla, CA 92093, USA. travasi@ucsd.edu.
⁴ d Director, Center for Renal Translational Medicine, UCSD/VA San Diego Health System, La Jolla, CA 92093-0711, USA. kusharma@ucsd.edu.

PMID: 30934387
DOI: 10.1586/eem.09.72

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.

Keywords: eEF2; eIF4E; kidney biopsy proteomics; kidney proteomics; mRNA processing; mRNA translation; phosphatase; pirfenidone; protein phosphorylation.