Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

H. Makino, M. Mukoyama, K. Mori, T. Suganami, M. Kasahara, K. Yahata, T. Nagae, H. Yokoi, K. Sawai, Yoshihiro Ogawa, S. Suga, Y. Yoshimasa, A. Sugawara, I. Tanaka, K. Nakao

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Aims/hypothesis: Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. Materials and methods: We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. Results: After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-β and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. Conclusions/interpretation: Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.

Original languageEnglish
Pages (from-to)2514-2524
Number of pages11
JournalDiabetologia
Volume49
Issue number10
DOIs
Publication statusPublished - Oct 1 2006
Externally publishedYes

Fingerprint

Brain Natriuretic Peptide
Diabetic Nephropathies
Natriuretic Peptides
Kidney
Mesangial Cells
Wounds and Injuries
Glucose
Experimental Diabetes Mellitus
Extracellular Matrix Proteins
Extracellular Signal-Regulated MAP Kinases
Glomerulonephritis
Hypertrophy
Transgenic Mice
Albumins
Cultured Cells
Up-Regulation
Animal Models
Hemodynamics

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Makino, H., Mukoyama, M., Mori, K., Suganami, T., Kasahara, M., Yahata, K., ... Nakao, K. (2006). Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice. Diabetologia, 49(10), 2514-2524. https://doi.org/10.1007/s00125-006-0352-y

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice. / Makino, H.; Mukoyama, M.; Mori, K.; Suganami, T.; Kasahara, M.; Yahata, K.; Nagae, T.; Yokoi, H.; Sawai, K.; Ogawa, Yoshihiro; Suga, S.; Yoshimasa, Y.; Sugawara, A.; Tanaka, I.; Nakao, K.

In: Diabetologia, Vol. 49, No. 10, 01.10.2006, p. 2514-2524.

Research output: Contribution to journalArticle

Makino, H, Mukoyama, M, Mori, K, Suganami, T, Kasahara, M, Yahata, K, Nagae, T, Yokoi, H, Sawai, K, Ogawa, Y, Suga, S, Yoshimasa, Y, Sugawara, A, Tanaka, I & Nakao, K 2006, 'Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice', Diabetologia, vol. 49, no. 10, pp. 2514-2524. https://doi.org/10.1007/s00125-006-0352-y
Makino, H. ; Mukoyama, M. ; Mori, K. ; Suganami, T. ; Kasahara, M. ; Yahata, K. ; Nagae, T. ; Yokoi, H. ; Sawai, K. ; Ogawa, Yoshihiro ; Suga, S. ; Yoshimasa, Y. ; Sugawara, A. ; Tanaka, I. ; Nakao, K. / Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice. In: Diabetologia. 2006 ; Vol. 49, No. 10. pp. 2514-2524.
@article{0c5430171b104eb4986c68a7f7557fc0,
title = "Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice",
abstract = "Aims/hypothesis: Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. Materials and methods: We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. Results: After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-β and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. Conclusions/interpretation: Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.",
author = "H. Makino and M. Mukoyama and K. Mori and T. Suganami and M. Kasahara and K. Yahata and T. Nagae and H. Yokoi and K. Sawai and Yoshihiro Ogawa and S. Suga and Y. Yoshimasa and A. Sugawara and I. Tanaka and K. Nakao",
year = "2006",
month = "10",
day = "1",
doi = "10.1007/s00125-006-0352-y",
language = "English",
volume = "49",
pages = "2514--2524",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "10",

}

TY - JOUR

T1 - Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

AU - Makino, H.

AU - Mukoyama, M.

AU - Mori, K.

AU - Suganami, T.

AU - Kasahara, M.

AU - Yahata, K.

AU - Nagae, T.

AU - Yokoi, H.

AU - Sawai, K.

AU - Ogawa, Yoshihiro

AU - Suga, S.

AU - Yoshimasa, Y.

AU - Sugawara, A.

AU - Tanaka, I.

AU - Nakao, K.

PY - 2006/10/1

Y1 - 2006/10/1

N2 - Aims/hypothesis: Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. Materials and methods: We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. Results: After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-β and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. Conclusions/interpretation: Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.

AB - Aims/hypothesis: Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. Materials and methods: We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. Results: After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-β and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. Conclusions/interpretation: Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.

UR - http://www.scopus.com/inward/record.url?scp=33748486664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748486664&partnerID=8YFLogxK

U2 - 10.1007/s00125-006-0352-y

DO - 10.1007/s00125-006-0352-y

M3 - Article

VL - 49

SP - 2514

EP - 2524

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 10

ER -