PMID- 16705144
OWN - NLM
STAT- MEDLINE
DCOM- 20070105
LR  - 20141120
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 291
IP  - 6
DP  - 2006 Dec
TI  - Spontaneous activation of the NF-kappaB signaling pathway in isolated normal 
      glomeruli.
PG  - F1169-76
AB  - In this report, we describe that NF-kappaB is spontaneously activated in 
      isolated, normal glomeruli. Ex vivo incubation of isolated rat glomeruli 
      triggered expression of a NF-kappaB-dependent gene, monocyte chemoattractant 
      protein-1 (MCP-1), in parallel with downregulation of IkappaBalpha and 
      IkappaBbeta proteins and activation of the p65 NF-kappaB subunit. The induction 
      of MCP-1 was also observed in mesangial cells coincubated with isolated glomeruli 
      or exposed to media conditioned by isolated glomeruli (GCM), which was abrogated 
      by inhibition of NF-kappaB. The activation of NF-kappaB by glomerulus-derived 
      factors was confirmed using reporter mesangial cells that produce secreted 
      alkaline phosphatase (SEAP) under the control of the kappaB enhancer element. 
      When the reporter cells were adoptively transferred into normal glomeruli, 
      expression of SEAP mRNA and activity of SEAP were also upregulated in the 
      explanted glomeruli. The molecular weight of factors responsible for activation 
      of NF-kappaB was >50 kDa, and TNF-alpha was identified as one of 
      glomerulus-derived activators. To examine upstream events involved, we focused on 
      MAP kinases that are spontaneously activated in explanted glomeruli. Selective 
      suppression of ERK or p38 MAP kinase significantly attenuated activation of 
      NF-kappaB in mesangial cells triggered by coculture with isolated glomeruli. 
      Interestingly, the suppressive effects by MAP kinase inhibitors were not observed 
      in mesangial cells treated with GCM. These data suggested that NF-kappaB was 
      spontaneously activated in explanted glomeruli via autocrine/paracrine factors 
      including TNF-alpha and that the production of NF-kappaB activators by glomeruli 
      was, at least in part, through MAP kinase pathways.
FAU - Hayakawa, Kunihiro
AU  - Hayakawa K
AD  - Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine 
      and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
FAU - Meng, Yiman
AU  - Meng Y
FAU - Hiramatsu, Nobuhiko
AU  - Hiramatsu N
FAU - Kasai, Ayumi
AU  - Kasai A
FAU - Yao, Jian
AU  - Yao J
FAU - Kitamura, Masanori
AU  - Kitamura M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060516
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Autocrine Communication/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - In Vitro Techniques
MH  - MAP Kinase Signaling System/*physiology
MH  - Male
MH  - Mesangial Cells/cytology/*metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Paracrine Communication/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factor RelA/*metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2006/05/18 09:00
MHDA- 2007/01/06 09:00
CRDT- 2006/05/18 09:00
PHST- 2006/05/18 09:00 [pubmed]
PHST- 2007/01/06 09:00 [medline]
PHST- 2006/05/18 09:00 [entrez]
AID - 00513.2005 [pii]
AID - 10.1152/ajprenal.00513.2005 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2006 Dec;291(6):F1169-76. doi: 
      10.1152/ajprenal.00513.2005. Epub 2006 May 16.