Renal C3 complement component: Feed forward to diabetic kidney disease

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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
Pages (from-to)48-56
Number of pages9
JournalAmerican Journal of Nephrology
Volume41
Issue number1
DOIs
StatePublished - Mar 19 2015

Fingerprint

Complement C3
Diabetic Nephropathies
Kidney
Complement Activation
Messenger RNA
Anaphylatoxin C5a Receptor
CD55 Antigens
Complement Membrane Attack Complex
Gene Regulatory Networks
Chronic Kidney Failure
Ischemia
Heart Failure
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Renal C3 complement component : Feed forward to diabetic kidney disease. / Kelly, Katherine; Liu, Yunlong; Zhang, Jizhong; Dominguez, Jesus.

In: American Journal of Nephrology, Vol. 41, No. 1, 19.03.2015, p. 48-56.

Research output: Contribution to journalArticle

@article{d01a776b44204e86b2243b1d3baaddc1,
title = "Renal C3 complement component: Feed forward to diabetic kidney disease",
abstract = "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.",
keywords = "Complement, Diabetic nephropathies, Ischemia, Kidney failure, chronic",
author = "Katherine Kelly and Yunlong Liu and Jizhong Zhang and Jesus Dominguez",
year = "2015",
month = "3",
day = "19",
doi = "10.1159/000371426",
language = "English",
volume = "41",
pages = "48--56",
journal = "American Journal of Nephrology",
issn = "0250-8095",
publisher = "S. Karger AG",
number = "1",

}

TY - JOUR

T1 - Renal C3 complement component

T2 - Feed forward to diabetic kidney disease

AU - Kelly, Katherine

AU - Liu, Yunlong

AU - Zhang, Jizhong

AU - Dominguez, Jesus

PY - 2015/3/19

Y1 - 2015/3/19

N2 - 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.

AB - 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.

KW - Complement

KW - Diabetic nephropathies

KW - Ischemia

KW - Kidney failure, chronic

UR - http://www.scopus.com/inward/record.url?scp=84923081915&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923081915&partnerID=8YFLogxK

U2 - 10.1159/000371426

DO - 10.1159/000371426

M3 - Article

C2 - 25662584

AN - SCOPUS:84923081915

VL - 41

SP - 48

EP - 56

JO - American Journal of Nephrology

JF - American Journal of Nephrology

SN - 0250-8095

IS - 1

ER -