Transcription factors in the pathogenesis of diabetic nephropathy

Amber Paratore Sanchez, Kumar Sharma

Research output: Contribution to journalReview article

95 Citations (Scopus)

Abstract

Approximately a third of patients with diabetes develop diabetic kidney disease, and diabetes is the leading cause of end-stage renal disease in most developed countries. Hyperglycaemia is known to activate genes that ultimately lead to extracellular matrix accumulation, the hallmark of diabetic nephropathy. Several transcription factors have been implicated in glucose-mediated expression of genes involved in diabetic nephropathy. This review focuses on the transcription factors upstream stimulatory factors 1 and 2 (USF1 and 2), activator protein 1 (AP-1), nuclear factor (NF)-κB, cAMP-response-element- binding protein (CREB), nuclear factor of activated T cells (NFAT), and stimulating protein 1 (Sp1). In response to high glucose, several of these transcription factors regulate the gene encoding the profibrotic cytokine transforming growth factor β, as well as genes for a range of other proteins implicated in inflammation and extracellular matrix turnover, including thrombospondin 1, the chemokine CCL2, osteopontin, fibronectin, decorin, plasminogen activator inhibitor 1 and aldose reductase. Identifying the molecular mechanisms by which diabetic nephropathy occurs has important clinical implications as therapies can then be tailored to target those at risk. Strategies to specifically target transcription factor activation and function may be employed to halt the progression of diabetic nephropathy.

Original languageEnglish (US)
Article numbere13
JournalExpert Reviews in Molecular Medicine
Volume11
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Fingerprint

Diabetic Nephropathies
Transcription Factors
Extracellular Matrix
Upstream Stimulatory Factors
Decorin
NFATC Transcription Factors
Thrombospondin 1
Glucose
Cyclic AMP Response Element-Binding Protein
Aldehyde Reductase
Osteopontin
Chemokine CCL2
Plasminogen Activator Inhibitor 1
Transcription Factor AP-1
Transforming Growth Factors
Oncogenes
Fibronectins
Developed Countries
Hyperglycemia
Transcriptional Activation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Transcription factors in the pathogenesis of diabetic nephropathy. / Sanchez, Amber Paratore; Sharma, Kumar.

In: Expert Reviews in Molecular Medicine, Vol. 11, e13, 01.12.2009.

Research output: Contribution to journalReview article

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