Extracellular roles of high - mobility - group B1
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1 Chinese Journal of Pathophysiology 2004,20 (4) : [ ] (2004) B1 3,, ( 304, ) Extracellular roles of high - mobility - group B1 WANG Zhong - tang, YAO Yong - ming, SHENG Zhi - yong ( Burns Institute, 304 th Hospital of PLA, Beijing , China) A Review High - mobility - group B1 (HMGB1), an abundant, highly conserved cellular protein, is widely known as a nuclear DNA - binding protein that stabilizes nucleosome formation, and facilitates gene tran2 scription. Recent studies suggested that HMGB1 could be overexpressed and released from cellular nucleosome upon endotoxin and cytokine stimulation, or other stress challenge including burns, shock, as well as infection. Therefore, extracellular HMGB1 might be involved in the pathogenesis of sepsis and subsequent multiple organ dysfunction syndrome. Moreover, experimental data showed that extracellular HMGB1 might play vital roles in nerves development, tumor metastasis, atherosclerosis and restenosis after vascular damage. [] ; ; ; ; [ KEY WORDS] High mobility group proteins ; Sepsis ; Neurites ; Neoplasm metastasis ; Arteriosclerosis [] R363 [] A ( high mobility group protein, HMG), DNA HMG :HMG - 1/ - 2 HMG - 14/ - 17 HMG - I ( Y) 2000 HMG HMGB1 DNA HMGB1 HMGA HMGB HMGN [1 ],, HMG,,,HMGB1 [2 ] B1 ( HMGB1) 30kD, 215, 1 HMGB1 HMGB1,, 100 %, TNF - IL %HMGB1 : HMG Box A ( multiple organ dysfunction syn2 HMG Box B,80-90, drome,mods) ( Tracey,1987 ; Bianchi,1996), TNF - IL - 1 [ ] [ ] [ ] ( No. G ) ; ( No ) ; (No. 98J013) Tel : ; E - mail : com ( - 43 %), ( - 20 ), DNA ;C - 30, (Fink,1995), 5 d, TNF - IL - 1 (Mari2 no,1997) ; TNF - (Amiot,1997), TNF -
2 HMGB1 [10 ],HMGB1, Wang [3 ],, RAW h, 30 kd,hmgb1raw GH 3 HMGB1 HMGB1, 6-8 h [11 ] HMGB1,TNF - IL - 1 RAW HMGB1 [3 ] 112 HMGB1 RAW,8 h HMGB1,16 h, h,hmgb1,[ 35 S] - 32 h [3 ], 12 h HMGB h HMGB1,12-36 h HMGB1,, 72 h [4,5 ] HMGB1 HMGB1 [3 ] TNF - IL - 1 HeLa 3T3,,, HMGB1 HMGB1, [6 ] HMGB1 [12 ], HMGB1, HMGB1 - / - HMGB1 + / + rhmgb1 ( 10-50g) TNF -,HMGB1 + / + Balb/ C,2 h [12 ] HMGB1,36 h 50 g,rhmgb1 ; ( C3H/ HeN) ( C3H/ HeJ ) rhmgb1 Wang [3 ], ( 500g), 16 h [3 ] HMGB1 10 mg/ L HMGB1 C3H/ HeJ,,TNF - [3 ], HMGB1, / CD14,,HMGB1 24 h, 72 h ;, HMGB1 ;,,, HMGB1,25 HMGB1 [4,5,7 ] HMGB1,HMGB1, HMGB1, HMGB1 72 h, [8,9 ] ( C3H/ HeJ ) [14 ] HMGB1 TNF - IL - 1 MIP h, HMGB1,,, TNF - IL - 1, TNF - [8 ] Sappington [9 ] HMGB1 B box inos NO, Caco - 2 HMGB1 TNF -,4h TNF -, 6 h,8-10 h, HMGB1, TNF - IL - 1,,, HMGB1 - / - [13 ], HMGB1 [3 ], HMGB1 113 HMGB1, [3 ], 24 h HMGB1,,, TNF - IL - 1 HMGB1, MODS
3 HMGB1, HMGB1 (lipopolysaccharide binding protein, LBP) HMGB1 CD14, [15 ] 2 HMGB1 LBP/ CD14 HMGB1,2 h, LBP/ CD14,( Rauvala, HMGB1 LBP/ CD14, LBP/ CD14 HMGB1,, HMGB1 HMGB1 [4,5 ] ( Rauvala ; Merenmines LBP, CD14, HMGB1 [5 ], rhmgb1 Balb/ C,90 %, [3 ] ;HMGB1,TNF - -, [10 ] Wang [3 ] HMGB1 / CD14,HMGB1, N18 [20 ],LBP/ CD14 HMGB1, / HMGB1 HMGB1 JAK/ STAT [16 ] 24 h STAT - 3, TNF -, HMGB1 HMGB1 (Borna disease virus, JAK/ STAT 115 HMGB1 HMGB1,P24 HMGB1, BDV P h HMGB1, HMGB1 ;,BDV P h 2 h 12 h HMGB1, 510 mg,210 mg 2 50 %, [3 ] (receptor of advanced glycation end,balb/ C products, RAGE), HMGB1 [8 ] HMGB1, ( Hori 1 [5,7,16-19 ], 015 h 4 h RAGE, HMGB1, TNF - (Merenmies ), [16 ],Toll 2,, IL - 10 [17 ], 3 HMGB1, HMGB1 [5,7,18,19 ] HMGB , 1988). 1991), HMGB1,mRNA,HMGB1,HMGB1 ; -, HMGB1 SBP - 1 (Sulfoglucuronyl carbohydrate binding protein), [21 ] HMGB1 BDV) P24 BDV HMGB1 [22 ] HMGB1 HMGB1 HMGB1 RAGE 1995) ; HMGB1, HMGB1, HMGB1 HMGB1,HMGB1
4 676 ( Pakkinen and Rauvala ; Pakkinen ), C6 SMC (Baggiolini ; van HMGB1mRNA HMGB1, Leeuwen ; Degryse ) HMGB1 HMGB1 ; HMGB1,60 % ; HMGB1, SMC,HMGB1, 1/ 10 ; HMGB1 80 % [20 ], HMGB1 [25 ], c - Met HMGB1,HMGB1 [23 ],,HMGB1 Taguchi [24 ],HMGB1 RAGE, RAGE RAGE (srage),c6 ;, 1997) Degryse [25 ] HMGB1 SMC,fMLP bfbf, SMC 015 h,,2 h ; HMGB1 A B A + B HMGB1, [25 ],, HMGB1 SMC,,SMC RAGE,HMGB1 A + B RAGE SMC SMC,RAGE HMGB1 ; SMC ERK,HMGB1 RAGE C6,RAGE SMC ERK1/ 2 ;,Lewis ERK MEK PD98059,, HMGB1 ERK, SMC srage, [24 ] [25 ],, HMGB1 RAGE HMGB1 RAGE, MAPK HMGB1 RAGE SMC,,MAPK,,HMGB1 5 HMGB1 [24 ],v - Ha - ras srage, (Leder 1 HMGB1 1990) ; HMGB1 C6 MAPK 10, HMGB1 p38( ERK1/ RAGE 2), DN - RAGE srage :RAGE 3 1 [24 ] ; HMGB1 RAGE Rho 1, V 2 GTP Cdc42 Rac ( Huttnen 11999), RAGE,( Hori Cdc42 Rac ;Neeper ; Hofman ;1), RAGE RAGE,,HMGB1 RAGE,;RAGE (AGE / S100- HMGB1), 4 HMGB1,p21 ras - B cdc42/, rac MAPKK [24,25 ], Schmidt (smooth muscle cells, SMC) [26 ],:RAGE,,,,,, ;,,SMC,, (Van Leeuwen ; Schwartz1
5 677 Fig 1 The pattern of interaction of RAGE and it s ligand (from Schmidt et al. J Clin Invest, 2001). srage: soluble RAGE; DN - RAGE: dominant negative RAGE. 1 RAGE - 6 HMGB1, HMGB1 [12 ] Surgery, 1999, 126 (2) : Scaffidi P, Misteli T, Bianchi M. Release of chromatin pro2 tein HMGB1 by necrotic cells triggers inflammation[j ]. Na2 ture, 2002, 418 (6894) : ? [13 ] Calogero SF, Grassi A, Aguzzi T, et al. The lack of chromo2 somal proteinhmg1 does not disrupt cell growth, but causes?, HMGB1 lethal hypoglycaemia in newborn mice[j ]. Nat Genet, 1999,, 22 (3) : MODS [ 14 ] Ombrellino M, Wang H, Ajemian MS, et al. Increased serum, concentrations of high - mobility - group protein 1 in haemor2 rhagic shock[j ]. Lancet, 1999, 354 (9188) : [ ] [1 ] Bianchi ME, Bltrame M. Upwardly mobile proteins. Work2 shop : the role of HMG proteins in chromatin structure, gene expression and neoplasia[j ]. EMBO Rep, 2000, 2 (1) : [2 ] Carvajal IM, Baron RM, Perrella MA. High - mobility group - I/ Y proteins : potential role in the pathophysiology of criti2 cal illnesses[j ]. Crit Care Med, 2002, 30 (Suppl) : S36 - S42. [3 ] Wang H, Bloom O, Zhang M, et al. HMG- 1 as a late me2 diator of endotoxin lethality in mice[j ]. Science, 1999, 285 (5425) : [4 ],,,. - 1 [J ]., 2001, 39 (2) : [5 ],,,. - 1 [J ]., 2002, 18 (9) : [6 ] Wang H, Yan H, Czura CJ, et al. HMGB1 as a late mediator of lethal systemic inflammation [J ]. Am J Respir Crit Care Med, 2001, 164 (10 pt1) : [7 ] Fang WH, Yao YM, Shi ZG, et al. The significance of changes in high mobility group - 1 protein mrna expression in rats after thermal injury[j ]. Shock, 2002, 17 (4) : [8 ] Abraham E, Arcaroli J, Carmody A, et al. Cutting edge : HMG- 1 as a mediator of acute lung inflammation[j ]. J Im2 munol, 2000, 165 (6) : [9 ] Sappington PL, Yang R, Yang H, et al. HMGB1 B box in2 creases the permeability of Caco - 2 enterocytic monolayers and impairs intestinal barrier function in mice [J ]. Gastroen2 terology,2002,123 (3) : [10 ] Andersson U, Wang H, Palmblad K, et al. High mobility group 1 protein ( HMG - 1) stimulates proinflammatory cy2 tokine synthesis in human monocytes[j ]. J Exp Med, 2000, 192 (4) : [11 ] Wang H, Vishnubhakat JM, Bloom O, et al. Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein - 1 by pituicytes[j ]. [15 ] Fang WH, Yao YM, Shi ZG, et al. Effect of recombinant bactericidal/ permeability - increasing protein on endotoxin translocation and lipopolysaccharide - binding protein/ CD14 expression in rats following thermal injury[j ]. Crit Care Med, 2001, 29 (7) : [16 ],,,. - 1 [J ]., 2002, 27 (9) : [17 ],,,. - 1 Toll 2 [J ]., 2003, 19 (1) : [18 ],,, [J ]., 2002, 27 (9) : [19 ],,,. - 1 [J ]., 2002, 17 (9) : [20 ] Fages C, Nolo R, Huttunen HJ, et al. Regulation of cell mi2 gration by amphoterin[j ]. J Cell Sci, 2000, 113 (pt 4) : [21 ] Chou DK, Evans J E, Jungalwala FB. Identity of nuclear high - mobility - group protein, HMG - 1, and sulfoglucuronyl carbohydrate - binding protein, SBP - 1, in brain [ J ]. J Neurochem, 2001, 77 (1) : [22 ] Kamitani W, Shoya Y, Kobayashi T, et al. Borna disease virus phosphoprotein binds a neurite outgrowth factor, ampho2 terin/ HMG- 1[J ]. J Virol, 2001, 75 (18) :
6 678 [23 ] Nestl A,Von - Stein OD,Zatloukal K, et al. Gene expression patterns associated with the metastatic phenotype in rodent and human tumors[j ]. Cancer Res, 2001, 61 (4) : [24 ] Taguchi A, Blood DC, del Toro G, et al. Blockage of RAGE - amphoterin signaling suppresses tumor growth and metasta2 sis[j ]. Nature, 2000, 405 (6784) : [25 ] Degryse B, Bonaldi T, Scaffidi P, et al. The high mobility group ( HMG) boxes of the nuclear protein HMGB1 induce chemotaxis and cytoskeleton reorganization in rat smooth mus2 cle cells[j ]. J Cell Biol, 2001, 152 (6) : [ 26 ] Schmidt AM, Yan SD, Yan SF, et al. The multiligand recep2 tor RAGE as a progression factor amplifying immune and in2 flammatory responses[j ]. J Clin Invest, 2001, 108 (7) :
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