Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury

T. Suganami, M. Mukoyama, A. Sugawara, K. Mori, T. Nagae, M. Kasahara, K. Yahata, H. Makino, Y. Fujinaga, Yoshihiro Ogawa, I. Tanaka, K. Nakao

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

One of major causes of end-stage renal disease is glomerulonephritis, the treatment of which remains difficult clinically. It has already been shown that transgenic mice that overexpress brain natriuretic peptide (BNP), with a potent vasorelaxing and natriuretic property, have ameliorated glomerular injury after subtotal nephrectomy. However, the role of natriuretic peptides in immune-mediated renal injury still remains unknown. Therefore, the effects of chronic excess of BNP on anti-glomerular basement membrane nephritis induced in BNP-transgenic mice (BNP-Tg) were investigated and the mechanisms how natriuretic peptides act on mesangial cells in vitro were explored. After induction of nephritis, severe albuminuria (∼21-fold above baseline), tissue damage, including mesangial expansion and cell proliferation, and functional deterioration developed in nontransgenic littermates. In contrast, BNP-Tg exhibited much milder albuminuria (approximately fourfold above baseline), observed only at the initial phase, and with markedly ameliorated histologic and functional changes. Up-regulation of transforming growth factor-β (TGF-β and monocyte chemoattractant protein-1 (MCP-1), as well as increased phosphorylation of extracellular signal-regulated kinase (ERK), were also significantly inhibited in the kidney of BNP-Tg. In cultured mesangial cells, natriuretic peptides counteracted the effects of angiotensin II with regard to ERK phosphorylation and fibrotic action. Because angiotensin II has been shown to play a pivotal role in the progression of nephritis through induction of TGF-β and MCP-1 that may be ERK-dependent, the protective effects of BNP are likely to be exerted, at least partly, by antagonizing the renin-angiotensin system locally. The present study opens a possibility of a novel therapeutic potential of natriuretic peptides for treating immune-mediated renal injury.

Original languageEnglish
Pages (from-to)2652-2663
Number of pages12
JournalJournal of the American Society of Nephrology
Volume12
Issue number12
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Brain Natriuretic Peptide
Natriuretic Peptides
Kidney
Mesangial Cells
Nephritis
Extracellular Signal-Regulated MAP Kinases
Wounds and Injuries
Albuminuria
Chemokine CCL2
Angiotensin II
Transgenic Mice
Phosphorylation
Glomerular Basement Membrane
Transforming Growth Factors
Renin-Angiotensin System
Glomerulonephritis
Nephrectomy
Chronic Kidney Failure
Cultured Cells
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Suganami, T., Mukoyama, M., Sugawara, A., Mori, K., Nagae, T., Kasahara, M., ... Nakao, K. (2001). Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury. Journal of the American Society of Nephrology, 12(12), 2652-2663.

Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury. / Suganami, T.; Mukoyama, M.; Sugawara, A.; Mori, K.; Nagae, T.; Kasahara, M.; Yahata, K.; Makino, H.; Fujinaga, Y.; Ogawa, Yoshihiro; Tanaka, I.; Nakao, K.

In: Journal of the American Society of Nephrology, Vol. 12, No. 12, 2001, p. 2652-2663.

Research output: Contribution to journalArticle

Suganami, T, Mukoyama, M, Sugawara, A, Mori, K, Nagae, T, Kasahara, M, Yahata, K, Makino, H, Fujinaga, Y, Ogawa, Y, Tanaka, I & Nakao, K 2001, 'Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury', Journal of the American Society of Nephrology, vol. 12, no. 12, pp. 2652-2663.
Suganami T, Mukoyama M, Sugawara A, Mori K, Nagae T, Kasahara M et al. Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury. Journal of the American Society of Nephrology. 2001;12(12):2652-2663.
Suganami, T. ; Mukoyama, M. ; Sugawara, A. ; Mori, K. ; Nagae, T. ; Kasahara, M. ; Yahata, K. ; Makino, H. ; Fujinaga, Y. ; Ogawa, Yoshihiro ; Tanaka, I. ; Nakao, K. / Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury. In: Journal of the American Society of Nephrology. 2001 ; Vol. 12, No. 12. pp. 2652-2663.
@article{1d2e6241239345cea60552c973b1e53b,
title = "Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury",
abstract = "One of major causes of end-stage renal disease is glomerulonephritis, the treatment of which remains difficult clinically. It has already been shown that transgenic mice that overexpress brain natriuretic peptide (BNP), with a potent vasorelaxing and natriuretic property, have ameliorated glomerular injury after subtotal nephrectomy. However, the role of natriuretic peptides in immune-mediated renal injury still remains unknown. Therefore, the effects of chronic excess of BNP on anti-glomerular basement membrane nephritis induced in BNP-transgenic mice (BNP-Tg) were investigated and the mechanisms how natriuretic peptides act on mesangial cells in vitro were explored. After induction of nephritis, severe albuminuria (∼21-fold above baseline), tissue damage, including mesangial expansion and cell proliferation, and functional deterioration developed in nontransgenic littermates. In contrast, BNP-Tg exhibited much milder albuminuria (approximately fourfold above baseline), observed only at the initial phase, and with markedly ameliorated histologic and functional changes. Up-regulation of transforming growth factor-β (TGF-β and monocyte chemoattractant protein-1 (MCP-1), as well as increased phosphorylation of extracellular signal-regulated kinase (ERK), were also significantly inhibited in the kidney of BNP-Tg. In cultured mesangial cells, natriuretic peptides counteracted the effects of angiotensin II with regard to ERK phosphorylation and fibrotic action. Because angiotensin II has been shown to play a pivotal role in the progression of nephritis through induction of TGF-β and MCP-1 that may be ERK-dependent, the protective effects of BNP are likely to be exerted, at least partly, by antagonizing the renin-angiotensin system locally. The present study opens a possibility of a novel therapeutic potential of natriuretic peptides for treating immune-mediated renal injury.",
author = "T. Suganami and M. Mukoyama and A. Sugawara and K. Mori and T. Nagae and M. Kasahara and K. Yahata and H. Makino and Y. Fujinaga and Yoshihiro Ogawa and I. Tanaka and K. Nakao",
year = "2001",
language = "English",
volume = "12",
pages = "2652--2663",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "12",

}

TY - JOUR

T1 - Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury

AU - Suganami, T.

AU - Mukoyama, M.

AU - Sugawara, A.

AU - Mori, K.

AU - Nagae, T.

AU - Kasahara, M.

AU - Yahata, K.

AU - Makino, H.

AU - Fujinaga, Y.

AU - Ogawa, Yoshihiro

AU - Tanaka, I.

AU - Nakao, K.

PY - 2001

Y1 - 2001

N2 - One of major causes of end-stage renal disease is glomerulonephritis, the treatment of which remains difficult clinically. It has already been shown that transgenic mice that overexpress brain natriuretic peptide (BNP), with a potent vasorelaxing and natriuretic property, have ameliorated glomerular injury after subtotal nephrectomy. However, the role of natriuretic peptides in immune-mediated renal injury still remains unknown. Therefore, the effects of chronic excess of BNP on anti-glomerular basement membrane nephritis induced in BNP-transgenic mice (BNP-Tg) were investigated and the mechanisms how natriuretic peptides act on mesangial cells in vitro were explored. After induction of nephritis, severe albuminuria (∼21-fold above baseline), tissue damage, including mesangial expansion and cell proliferation, and functional deterioration developed in nontransgenic littermates. In contrast, BNP-Tg exhibited much milder albuminuria (approximately fourfold above baseline), observed only at the initial phase, and with markedly ameliorated histologic and functional changes. Up-regulation of transforming growth factor-β (TGF-β and monocyte chemoattractant protein-1 (MCP-1), as well as increased phosphorylation of extracellular signal-regulated kinase (ERK), were also significantly inhibited in the kidney of BNP-Tg. In cultured mesangial cells, natriuretic peptides counteracted the effects of angiotensin II with regard to ERK phosphorylation and fibrotic action. Because angiotensin II has been shown to play a pivotal role in the progression of nephritis through induction of TGF-β and MCP-1 that may be ERK-dependent, the protective effects of BNP are likely to be exerted, at least partly, by antagonizing the renin-angiotensin system locally. The present study opens a possibility of a novel therapeutic potential of natriuretic peptides for treating immune-mediated renal injury.

AB - One of major causes of end-stage renal disease is glomerulonephritis, the treatment of which remains difficult clinically. It has already been shown that transgenic mice that overexpress brain natriuretic peptide (BNP), with a potent vasorelaxing and natriuretic property, have ameliorated glomerular injury after subtotal nephrectomy. However, the role of natriuretic peptides in immune-mediated renal injury still remains unknown. Therefore, the effects of chronic excess of BNP on anti-glomerular basement membrane nephritis induced in BNP-transgenic mice (BNP-Tg) were investigated and the mechanisms how natriuretic peptides act on mesangial cells in vitro were explored. After induction of nephritis, severe albuminuria (∼21-fold above baseline), tissue damage, including mesangial expansion and cell proliferation, and functional deterioration developed in nontransgenic littermates. In contrast, BNP-Tg exhibited much milder albuminuria (approximately fourfold above baseline), observed only at the initial phase, and with markedly ameliorated histologic and functional changes. Up-regulation of transforming growth factor-β (TGF-β and monocyte chemoattractant protein-1 (MCP-1), as well as increased phosphorylation of extracellular signal-regulated kinase (ERK), were also significantly inhibited in the kidney of BNP-Tg. In cultured mesangial cells, natriuretic peptides counteracted the effects of angiotensin II with regard to ERK phosphorylation and fibrotic action. Because angiotensin II has been shown to play a pivotal role in the progression of nephritis through induction of TGF-β and MCP-1 that may be ERK-dependent, the protective effects of BNP are likely to be exerted, at least partly, by antagonizing the renin-angiotensin system locally. The present study opens a possibility of a novel therapeutic potential of natriuretic peptides for treating immune-mediated renal injury.

UR - http://www.scopus.com/inward/record.url?scp=0035203499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035203499&partnerID=8YFLogxK

M3 - Article

C2 - 11729234

AN - SCOPUS:0035203499

VL - 12

SP - 2652

EP - 2663

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 12

ER -