PMID- 20231821
OWN - NLM
STAT- MEDLINE
DCOM- 20100707
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 90
IP  - 6
DP  - 2010 Jun
TI  - High-mobility group box-1 protein promotes granulomatous nephritis in 
      adenine-induced nephropathy.
PG  - 853-66
LID - 10.1038/labinvest.2010.64 [doi]
AB  - Granulomatous nephritis can be triggered by diverse factors and results in kidney 
      failure. However, despite accumulating data about granulomatous inflammation, 
      pathogenetic mechanisms in nephritis remain unclear. The DNA-binding 
      high-mobility group box-1 protein (HMGB1) initiates and propagates inflammation 
      when released by activated macrophages, and functions as an 'alarm cytokine' 
      signaling tissue damage. In this study, we showed elevated HMGB1 expression in 
      renal granulomas in rats with crystal-induced granulomatous nephritis caused by 
      feeding an adenine-rich diet. HMGB1 levels were also raised in urine and serum, 
      as well as in monocyte chemoattractant protein-1 (MCP-1), a mediator of 
      granulomatous inflammation. Injection of HMGB1 worsened renal function and 
      upregulated MCP-1 in rats with crystal-induced granulomatous nephritis. HMGB1 
      also induced MCP-1 secretion through mitogen-activated protein kinase (MAPK) and 
      phosphoinositide-3-kinase (PI3K) pathways in rat renal tubular epithelial cells 
      in vitro. Hmgb1(+/-) mice with crystal-induced nephritis displayed reduced MCP-1 
      expression in the kidneys and in urine and the number of macrophages in the 
      kidneys was significantly decreased. We conclude that HMGB1 is a new mediator 
      involved in crystal-induced nephritis that amplifies granulomatous inflammation 
      in a cycle where MCP-1 attracts activated macrophages, resulting in excessive and 
      sustained HMGB1 release. HMGB1 could be a novel target for inhibiting chronic 
      granulomatous diseases.
FAU - Oyama, Yoko
AU  - Oyama Y
AD  - Department of Laboratory and Vascular Medicine, Kagoshima University Graduate 
      School of Medical and Dental Sciences, Kagoshima, Japan.
FAU - Hashiguchi, Teruto
AU  - Hashiguchi T
FAU - Taniguchi, Noboru
AU  - Taniguchi N
FAU - Tancharoen, Salunya
AU  - Tancharoen S
FAU - Uchimura, Tomonori
AU  - Uchimura T
FAU - Biswas, Kamal K
AU  - Biswas KK
FAU - Kawahara, Ko-Ichi
AU  - Kawahara K
FAU - Nitanda, Takao
AU  - Nitanda T
FAU - Umekita, Yoshihisa
AU  - Umekita Y
FAU - Lotz, Martin
AU  - Lotz M
FAU - Maruyama, Ikuro
AU  - Maruyama I
LA  - eng
GR  - R01 AR056026/AR/NIAMS NIH HHS/United States
GR  - R01 AR056026-02/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100315
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (HMGB1 Protein)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/*pharmacology
MH  - Animals
MH  - Blood Urea Nitrogen
MH  - Chemokine CCL2/drug effects/genetics
MH  - Creatinine/blood
MH  - Epithelial Cells/cytology/physiology
MH  - Granuloma/*chemically induced/genetics/pathology/prevention & control
MH  - HMGB1 Protein/deficiency/*genetics/metabolism/pharmacology
MH  - Inflammation/chemically induced/genetics/pathology/prevention & control
MH  - Kidney Diseases/*chemically induced/pathology
MH  - Kidney Tubules/cytology/physiology
MH  - Mice
MH  - Nephritis/*chemically induced/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats
PMC - PMC3096665
MID - NIHMS290203
EDAT- 2010/03/17 06:00
MHDA- 2010/07/08 06:00
PMCR- 2011/05/17
CRDT- 2010/03/17 06:00
PHST- 2010/03/17 06:00 [entrez]
PHST- 2010/03/17 06:00 [pubmed]
PHST- 2010/07/08 06:00 [medline]
PHST- 2011/05/17 00:00 [pmc-release]
AID - S0023-6837(22)02478-3 [pii]
AID - 10.1038/labinvest.2010.64 [doi]
PST - ppublish
SO  - Lab Invest. 2010 Jun;90(6):853-66. doi: 10.1038/labinvest.2010.64. Epub 2010 Mar 
      15.