PMID- 11729234
OWN - NLM
STAT- MEDLINE
DCOM- 20020212
LR  - 20210513
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 12
IP  - 12
DP  - 2001 Dec
TI  - Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated 
      renal injury.
PG  - 2652-2663
LID - 10.1681/ASN.V12122652 [doi]
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 (approximately 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-beta (TGF-beta) 
      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-beta 
      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.
FAU - Suganami, Takayoshi
AU  - Suganami T
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Mukoyama, Masashi
AU  - Mukoyama M
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Sugawara, Akira
AU  - Sugawara A
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Mori, Kiyoshi
AU  - Mori K
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Nagae, Tetsuya
AU  - Nagae T
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Kasahara, Masato
AU  - Kasahara M
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Yahata, Kensei
AU  - Yahata K
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Makino, Hisashi
AU  - Makino H
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Fujinaga, Yuriko
AU  - Fujinaga Y
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Ogawa, Yoshihiro
AU  - Ogawa Y
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Tanaka, Issei
AU  - Tanaka I
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
FAU - Nakao, Kazuwa
AU  - Nakao K
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Kyoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Complement C3)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Natriuretic Agents)
RN  - 0 (Serum Albumin)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 26NAK24LS8 (Hydralazine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Albuminuria/urine
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Blood Pressure/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Complement C3/metabolism
MH  - Glomerular Mesangium/cytology/metabolism
MH  - Hydralazine/pharmacology
MH  - Immunoglobulin G/metabolism
MH  - Kidney/metabolism/pathology
MH  - Kidney Diseases/*immunology/metabolism/*pathology
MH  - Kidney Glomerulus/metabolism
MH  - Macrophages/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Natriuretic Agents/metabolism
MH  - Natriuretic Peptide, Brain/*pharmacology
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Serum Albumin/analysis
MH  - Transforming Growth Factor beta/metabolism
MH  - Transforming Growth Factor beta1
EDAT- 2001/12/01 10:00
MHDA- 2002/02/13 10:01
CRDT- 2001/12/01 10:00
PHST- 2001/12/01 10:00 [pubmed]
PHST- 2002/02/13 10:01 [medline]
PHST- 2001/12/01 10:00 [entrez]
AID - 12/12/2652 [pii]
AID - 10.1681/ASN.V12122652 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2001 Dec;12(12):2652-2663. doi: 10.1681/ASN.V12122652.