Novel systems biology insights using antifibrotic approaches for diabetic kidney disease

Satish P. RamachandraRao, Priti Talwar, Timothy Ravasi, Kumar Sharma

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)127-135
Number of pages9
JournalExpert Review of Endocrinology and Metabolism
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Keywords

  • EEF2
  • EIF4E
  • Kidney biopsy proteomics
  • Kidney proteomics
  • MRNA processing
  • MRNA translation
  • Phosphatase
  • Pirfenidone
  • Protein phosphorylation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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