Comprehensive genomic profiling in diabetic nephropathy reveals the predominance of proinflammatory pathways

Katherine Kelly, Yunlong Liu, Jizhong Zhang, Chirayu Goswami, Hai Lin, Jesus Dominguez

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Despite advances in the treatment of diabetic nephropathy (DN), currently available therapies have not prevented the epidemic of progressive chronic kidney disease (CKD). The morbidity of CKD, and the inexorable increase in the prevalence of end-stage renal disease, demands more effective approaches to prevent and treat progressive CKD. We undertook next-generation sequencing in a rat model of diabetic nephropathy to study in depth the pathogenic alterations involved in DN with progressive CKD. We employed the obese, diabetic ZS rat, a model that develops diabetic nephropathy, characterized by progressive CKD, inflammation, and fibrosis, the hallmarks of human disease. We then used RNA-seq to examine the combined effects of renal cells and infiltrating inflammatory cells acting as a pathophysiological unit. The comprehensive systems biology analysis of progressive CKD revealed multiple interactions of altered genes that were integrated into morbid networks. These pathological gene assemblies lead to renal inflammation and promote apoptosis and cell cycle arrest in progressive CKD. Moreover, in what is clearly a major therapeutic challenge, multiple and redundant pathways were found to be linked to renal fibrosis, a major cause of kidney loss. We conclude that systems biology applied to progressive CKD in DN can be used to develop novel therapeutic strategies directed to restore critical anomalies in affected gene networks.

Original languageEnglish
Pages (from-to)710-719
Number of pages10
JournalPhysiological Genomics
Volume45
Issue number16
DOIs
StatePublished - Aug 15 2013

Fingerprint

Diabetic Nephropathies
Chronic Renal Insufficiency
Kidney
Systems Biology
Fibrosis
Inflammation
Gene Regulatory Networks
Cell Cycle Checkpoints
Genes
Chronic Kidney Failure
Therapeutics
RNA
Apoptosis
Morbidity

Keywords

  • Diabetic nephropathies
  • Inflammation
  • Renal failure

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Comprehensive genomic profiling in diabetic nephropathy reveals the predominance of proinflammatory pathways. / Kelly, Katherine; Liu, Yunlong; Zhang, Jizhong; Goswami, Chirayu; Lin, Hai; Dominguez, Jesus.

In: Physiological Genomics, Vol. 45, No. 16, 15.08.2013, p. 710-719.

Research output: Contribution to journalArticle

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