Renal iron overload in rats with diabetic nephropathy

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Diabetic nephropathy (DN) remains incurable and is the main cause of endstage renal disease. We approached the pathophysiology of DN with systems biology, and a comprehensive profile of renal transcripts was obtained with RNA-Seq in ZS (F1 hybrids of Zucker and spontaneously hypertensive heart failure) rats, a model of diabetic nephropathy. We included sham-operated lean control rats (LS), sham-operated diabetic (DS), and diabetic rats with induced renal ischemia (DI). Diabetic nephropathy in DI was accelerated by the single episode of renal ischemia. This progressive renal decline was associated with renal iron accumulation, although serum and urinary iron levels were far lower in DI than in LS. Furthermore, obese/diabetic ZS rats have severe dyslipidemia, a condition that has been linked to hepatic iron overload. Hence, we tested and found that the fatty acids oleic acid and palmitate stimulated iron accumulation in renal tubular cells in vitro. Renal mRNAs encoding several key proteins that promote iron accumulation were increased in DI. Moreover, renal mRNAs encoding the antioxidant proteins superoxide dismutase, catalase, and most of the glutathione synthetic system were suppressed, which would magnify the prooxidant effects of renal iron loads. Substantial renal iron loads occur in obese/diabetic rats. We propose that in diabetes, specific renal gene activation is partly responsible for iron accumulation. This state might be further aggravated by lipid-stimulated iron uptake. We suggest that progressive renal iron overload may further advance renal injury in obese/diabetic ZS rats.

Original languageEnglish (US)
Article numbere12654
JournalPhysiological Reports
Volume3
Issue number12
DOIs
StatePublished - 2015

Fingerprint

Iron Overload
Diabetic Nephropathies
Kidney
Iron
Ischemia
Messenger RNA
Systems Biology
Palmitates
Oleic Acid
Dyslipidemias
Catalase
Transcriptional Activation
Superoxide Dismutase
Glutathione

Keywords

  • Chronic
  • Complement
  • Diabetic nephropathies
  • Ischemia
  • Kidney failure

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Renal iron overload in rats with diabetic nephropathy. / Dominguez, Jesus; Liu, Yunlong; Kelly, Katherine.

In: Physiological Reports, Vol. 3, No. 12, e12654, 2015.

Research output: Contribution to journalArticle

@article{ef8def7f24e8411d853ee761ec7075f7,
title = "Renal iron overload in rats with diabetic nephropathy",
abstract = "Diabetic nephropathy (DN) remains incurable and is the main cause of endstage renal disease. We approached the pathophysiology of DN with systems biology, and a comprehensive profile of renal transcripts was obtained with RNA-Seq in ZS (F1 hybrids of Zucker and spontaneously hypertensive heart failure) rats, a model of diabetic nephropathy. We included sham-operated lean control rats (LS), sham-operated diabetic (DS), and diabetic rats with induced renal ischemia (DI). Diabetic nephropathy in DI was accelerated by the single episode of renal ischemia. This progressive renal decline was associated with renal iron accumulation, although serum and urinary iron levels were far lower in DI than in LS. Furthermore, obese/diabetic ZS rats have severe dyslipidemia, a condition that has been linked to hepatic iron overload. Hence, we tested and found that the fatty acids oleic acid and palmitate stimulated iron accumulation in renal tubular cells in vitro. Renal mRNAs encoding several key proteins that promote iron accumulation were increased in DI. Moreover, renal mRNAs encoding the antioxidant proteins superoxide dismutase, catalase, and most of the glutathione synthetic system were suppressed, which would magnify the prooxidant effects of renal iron loads. Substantial renal iron loads occur in obese/diabetic rats. We propose that in diabetes, specific renal gene activation is partly responsible for iron accumulation. This state might be further aggravated by lipid-stimulated iron uptake. We suggest that progressive renal iron overload may further advance renal injury in obese/diabetic ZS rats.",
keywords = "Chronic, Complement, Diabetic nephropathies, Ischemia, Kidney failure",
author = "Jesus Dominguez and Yunlong Liu and Katherine Kelly",
year = "2015",
doi = "10.14814/phy2.12654",
language = "English (US)",
volume = "3",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "John Wiley and Sons Inc.",
number = "12",

}

TY - JOUR

T1 - Renal iron overload in rats with diabetic nephropathy

AU - Dominguez, Jesus

AU - Liu, Yunlong

AU - Kelly, Katherine

PY - 2015

Y1 - 2015

N2 - Diabetic nephropathy (DN) remains incurable and is the main cause of endstage renal disease. We approached the pathophysiology of DN with systems biology, and a comprehensive profile of renal transcripts was obtained with RNA-Seq in ZS (F1 hybrids of Zucker and spontaneously hypertensive heart failure) rats, a model of diabetic nephropathy. We included sham-operated lean control rats (LS), sham-operated diabetic (DS), and diabetic rats with induced renal ischemia (DI). Diabetic nephropathy in DI was accelerated by the single episode of renal ischemia. This progressive renal decline was associated with renal iron accumulation, although serum and urinary iron levels were far lower in DI than in LS. Furthermore, obese/diabetic ZS rats have severe dyslipidemia, a condition that has been linked to hepatic iron overload. Hence, we tested and found that the fatty acids oleic acid and palmitate stimulated iron accumulation in renal tubular cells in vitro. Renal mRNAs encoding several key proteins that promote iron accumulation were increased in DI. Moreover, renal mRNAs encoding the antioxidant proteins superoxide dismutase, catalase, and most of the glutathione synthetic system were suppressed, which would magnify the prooxidant effects of renal iron loads. Substantial renal iron loads occur in obese/diabetic rats. We propose that in diabetes, specific renal gene activation is partly responsible for iron accumulation. This state might be further aggravated by lipid-stimulated iron uptake. We suggest that progressive renal iron overload may further advance renal injury in obese/diabetic ZS rats.

AB - Diabetic nephropathy (DN) remains incurable and is the main cause of endstage renal disease. We approached the pathophysiology of DN with systems biology, and a comprehensive profile of renal transcripts was obtained with RNA-Seq in ZS (F1 hybrids of Zucker and spontaneously hypertensive heart failure) rats, a model of diabetic nephropathy. We included sham-operated lean control rats (LS), sham-operated diabetic (DS), and diabetic rats with induced renal ischemia (DI). Diabetic nephropathy in DI was accelerated by the single episode of renal ischemia. This progressive renal decline was associated with renal iron accumulation, although serum and urinary iron levels were far lower in DI than in LS. Furthermore, obese/diabetic ZS rats have severe dyslipidemia, a condition that has been linked to hepatic iron overload. Hence, we tested and found that the fatty acids oleic acid and palmitate stimulated iron accumulation in renal tubular cells in vitro. Renal mRNAs encoding several key proteins that promote iron accumulation were increased in DI. Moreover, renal mRNAs encoding the antioxidant proteins superoxide dismutase, catalase, and most of the glutathione synthetic system were suppressed, which would magnify the prooxidant effects of renal iron loads. Substantial renal iron loads occur in obese/diabetic rats. We propose that in diabetes, specific renal gene activation is partly responsible for iron accumulation. This state might be further aggravated by lipid-stimulated iron uptake. We suggest that progressive renal iron overload may further advance renal injury in obese/diabetic ZS rats.

KW - Chronic

KW - Complement

KW - Diabetic nephropathies

KW - Ischemia

KW - Kidney failure

UR - http://www.scopus.com/inward/record.url?scp=85005976093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85005976093&partnerID=8YFLogxK

U2 - 10.14814/phy2.12654

DO - 10.14814/phy2.12654

M3 - Article

AN - SCOPUS:85005976093

VL - 3

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 12

M1 - e12654

ER -