Renal C3 complement component: Feed forward to diabetic kidney disease

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21 Scopus citations


Background: Diabetic nephropathy is the main cause of end-stage renal disease and has reached epidemic proportions. Methods: Comprehensive genomic profiling (RNAseq) was employed in the ZS (F1 hybrids of Zucker and spontaneously hypertensive heart failure) model of diabetic nephropathy. Controls were lean littermates. Results: Diabetic nephropathy in obese, diabetic ZS was accelerated by a single episode of renal ischemia (DI). This rapid renal decline was accompanied by the activation of the renal complement system in DI, and to a lesser extent in sham-operated diabetic rats (DS). In DI there were significant increases in renal mRNA encoding C3, C4, C5, C6, C8, and C9 over sham-operated lean normal controls (LS). Moreover, mRNAs encoding the receptors for the anaphylatoxins C3a and C5a were also significantly increased in DI compared to LS. The classic complement pathway was activated in diabetic kidneys with significant increases of C1qa, C1qb, and C1qc mRNAs in DI over LS. In addition, critical regulators of complement activation were significantly attenuated in DI and DS. These included mRNAs encoding CD55, decay accelerating factor, and CD59, which inhibit the membrane attack complex. C3, C4, and C9 proteins were demonstrated in renal tubules and glomeruli. The complement RNAseq data were incorporated into a gene network showing interactions among C3-generating renal tubular cells and other immune competent migratory cells. Conclusions: We conclude that local activation of the complement system mediates renal injury in diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)48-56
Number of pages9
JournalAmerican journal of nephrology
Issue number1
StatePublished - Mar 19 2015


  • Complement
  • Diabetic nephropathies
  • Ischemia
  • Kidney failure, chronic

ASJC Scopus subject areas

  • Nephrology

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