亲环素A和CD147在皮肤衰老过程中表达的研究_英文_

亲环素A和CD147在皮肤衰老过程中表达的研究_英文_ Expression of cyclophilin A and CD147 during skin aging 1 1 1 2 1 1 1LI Ji,XIE Hongfu,YI Mei,PENG Lefang,LEI Dan,CHEN Xiang,JIAN Dan ( 1, Department Doefr matology,Xiangya Hospital,Central SouthU niversity,Changsha 41000;8 2, Department Eofe ctrocardogram,Hunan Provnca Peopes Hospta of Hunan,Changsha 41000,5liiillil’ China) Abstract:bjectiveO To nvestgate the roe of cycophn A ( CypA) and CD147 in iillili the process ofk ns Twenty cases tofss ue sampes from junor group ( ，15 yearsiili aging, Methods old) ,middle age grou( p30 , 40 yearsol d) or old age group( ， 65 yearsol d) were collected from photophobic and exposal parts ofk isn,respectively, Immunohistochemistry ( IHC) and in situ hy- bridization ( ISH) were carried out tos emi-quantitatively detect thex preession level of CyPA and CD147, Results IHC demonstrated that CboyPtA h and CD147 were expreissn boedt hp hotophobic and exposal parts ofno rmal human ksin in all 3g roups, The expression levels of both CyPA and CD147 werein creased with increase in age, There werei gnsificant differences in both CyPA and Key words:CyPA;CD147; skin aging CD147 expression among 3 groups( P ， 0, 05) , CyPA and CD147 waerelso positively correlated in all 3 groups, Similar results were cahieved by ISH, Conclusion The interaction betweenC D147 and CyPA might play an important role in the process ofki n saging, CD147A 亲环素 和在皮肤衰老过程中 表达的 研究 1 1 1 2 1 1 1,,,,,,李吉谢红付易梅彭乐芳雷丹陈翔简丹 ( 1, ,410008; 2, ,41000)5中南大学湘雅医院皮肤科长沙 湖南省人民医院心电图室长沙 ,, : A( CyPA) CD147 摘要目的检测不同年龄组正常人避光部位及曝光部位表皮组织中亲环素 和 的表 ,CyPA CD147 ， 15 30 , 40 。: ( ) 、( ) 达初步探讨 和 在皮肤衰老过程中的意义方法收集少年组岁中年组岁和 ( ， 65 20 2 ) ,老年组岁避光部位和曝光部位正常皮肤各 例运用免疫组织化学及原位杂交 种方法检测表皮中 CyPA CD147 mRNA CyPA CD147 ,。和 蛋白和 的 表 达 水 平并 分 析 各 年 龄 组 和 的 表 达 水 平 的 差 异 及 相 关 性 : CyPA CD147 2 ,,结果免疫组织化学结果显示 和 种蛋白在曝光和避光部位都为老年组最高中年组次之少年 ,( P ，0 , 05) ,CyPA CD147 =( r 组最低各组间差异具有统计学意义 均 且各组中 和 表达呈正相关 避光 部 位 0, 899,r = 0, 945) 。CyPA CD147 mRNA 曝光部位 组织原位杂交结果显示 和 在曝光和避光部位都为老年组最 ,,,( P ， 0, 05) ,CyPA CD147 高中年组次之少年组最低各组间差异具有统计学意义均 且各组中 和 表达呈正 ( r = 0, 792,r = 0, 782) 。: CyPA CD147 相关避光部位 曝光部位 结论和 相互作用可能在皮肤衰老过程中起重 。 要作用 ,, A; CD147; 关键词亲环素 皮肤衰老 DOI: 10, 3969 / j, issn, 1672-7347, 2011, 03, 003 Date of ecepon 2010 , 10 , 25rti Bogaphy LI Ji,M, D, ,attending physician,mainly engagedin the study okfi n saging and epidermal stem cells,ir Corresponding author JIAN Dan,E-mail: jjdd770@ ohtmail, com Foundation items This work was supported byNa titheona l Natural Science Foundation of China for Youth( 30800992 ) and Scientific Re- search Fund from the Departmecintenc e oafnd S Technology of HunanP rovince,P, R, China ( 2010FJ315)5 , Skin aging is classified into endogenous and tect neurons foromxid ative damages by way xoftra -e ex-cellular regulated protein kinases ( ERK ) ,1,ogenous g iang, It is shown in theexi sting 1 /2 re- signaling pathway, It was founidn our early study,2, ,24,searchthat theo xidative stress caused by reathec- tive oxygen pescies ( ROS) generatedi n thep rocess that CD147 can protectm atliheg nant melanoma cell of cell metabolism is one of the moismtpo rtant line A375 fromo xidative stress caused Hby 2 cau- O,2 ses of kisn intrinsic aging, As thes kin is the Therefor,ewe speculated that theco mbined action of outer- CyPA and CD147 pl ays an important part in t he mostl ayer of theb ody,it is directly affected by process ofl oswing down ksin aging by inhibiting envi- oxi- ronmenta factors such oasxyg en,utravoet ( UV)llil dative stress, Howeve,r no relevant reports and soo n, The skn ces can beo xdzed illiihave directly, been published yet, or absorbUV and convert tlheumi nous energyi nto The aging of peidermis is thought to be one chemical energy, producing large amount of RO S of ,3,and causing oxidative stress, The excessive ROS the mosti mportant reasons fork ins aging because produced by the endogenous and fexogenousactors it will cause idrect damages tvo ari ous plays an important role in skin moisturizing and biomacromole skin ,25,cules such asp rotein,lipid,and nucleic acidbarrier, In ourea rly study,change of ,4,, expression ,5-and ifnally lead to dysfunction and aging of cellslevel of many olmecules was foundin aged 1 MATERIALS AND METHODS7,, skin, In It can beco ncluded from the above facts ktihatn s 1, 1 Materialsthe presentre search,in order to study the in- 1, 1, 1 Subjectspossible We collected the normal skin from the kisn- trinsic aging has the samoel ecmular mechanism as effect ofCy PA and CD147 itnhe process ofki n sag- grafting or ksin flap grafting surgeries of 120 ,3,8-9, photoaging,B oth of them are affectoedxid aby- ing,we detectedth eir protein and mRNA expressionpatients who had beendia gnosed of noc hronic systemic or lo- cal skin disease,s All the patients were tive stress caused RbyOS, which brings a sreies of levels in normal skin keratinocyte ( KC) from hsaded from Depart- ment ofP lastic Surgery and Department ,10,subsequent effect,sand influences the ksin and exposed body partosun gof, miyddle-aged,and of Skin Sur- gery, Xiangya Hospital, Central ag- South U niversity old people,using immunohistochemical method nad ing,( Changsha,China) , The 120 atpients were divided in-situ hybridization, Cyclophilin A ( CyPA) ,a member of tihemm u-into the junior group( ，15 yearsol d) ,the nophilin family,is the mian receptor of tihemmun emiddle inhibitor cyclosporine A ( CsA) , It has the age group( between 30 and 40 yearsold) , and the activityold age group ( ，65 yearsol d) ,respectively, The of peptidyl prolyl cis-trans isomerase,and can skin was taken from the shaded partpsa tiofent s20 cata-in each grou,pand exposed parts of the othera- 20 p lyze protein folding and transferencein cells, In tients, Here,the shaded parts referredabd otmoe n re-and the inn er side of the th igh,and the cent years,it has been found thati ntcrhe eas e exposedbelongingto the i mmunoglobulin , ? ofsuperfamyilparts referred to facene candk, ( IGSF) ,which has a olmecular weight of about 58 ,18,CyPA in cancere llcs can reduce the cell In thej unior group,providers of skin from kD,CD147 distributes widely in body,and is apoptosisni-sha- volved in various physiological and ,11,induced by oxidative stress, CyPA can pathologicalded partsi ncluded 10 males and 10 efmales,with ,19-21,protectprocesses, CD147 ist he cell surface receptor age of( 9, 2 ? 3, 4) years old,and providers of ,12-cells from oxidative stressi n various wayssofkin 14,, InCyPA,and plays an important role in CyPA-media-from exposed parintcsl uded 11 males and 9 efmales, the state ofoxi dative stres,sthe expression of CyPAted isgnal transmission and chemotactic activitywith age of( 9, 8 ?4 , 5 ) years old; in the 3, 1) years old,and providers of ksin from xeposedtime and then addedwit h enzyme-labeled anti-rabbit partsi ncluded 11 males and 9 efmales,with age fopolymer and incubated at 37? for 20 m in, The ( 34, 5 ? 3, 0) years old; in theo ld age rgoup,slices were washedwi th PBS for 3ti mes,5 min each pro-time again beforeDA B color development was per- formed, After color was developed,the tissue viders of ksin from shaded parintcsl uded 10 slicesmales and 10 efmaes,wth age of ( 71, 0 ?3 , 2 ) liwere washed wit h running water and coun terstained yearswith hematoxylin ( HE) for 3 min, Then yhdrochlo- old,and providers of ksin from exposed part ric acid / alcohol differentiation was done includ-followed by ed 10 males and 10 efmales,with age of( 69, 8 ?routine washing,dehydration,vitrification,and slide3, 6) yearso ld, In each grou,tphe age of opvirders of skn from shaded parts was gnotnf csanty iiiilcovering, The result was observedwi th optical differ-micro-Immunohistochemical primary antibodyrabbit anti-human CD147 polyclonal antibody and SP im-scope,the opsitive cells were count,edand pohto-ent from those from exposed( Ppar ， 0t,s 05 ) ,and the ratio of mlae to female in each group was not munohistochemical staining kit were purchased from graphs weretak en, PBS bufferin replacement of the sBieig-jing Zhongshan Go ldenbrige Bio-technique Co,primary antibody serves as tnheeg ative control, nificantly different ( P ， 0, 05) ,Ltd, ( China ) ; rabbit anti-human CyPA 1, 2, 2 In-situ hybridization The yhbridization was performed tr ictsly 1po, l1y,c 2l onaMalin equipments and reagentsa thickness 8 m, andset on the μ follow- ing the instructions of thek it, The skin ofdedicated slides, The t issue slices were f ixed with antibody was from Abcam Cor poration in theU SA;tissues pre- servedi n liquid nitrogen was embedded with OCT embedding medium,series-sectioned at , 4%CD147 in-situ hybridization kit was bought fromWu- 20 ? into paraformaldehyde at room temperature for 20 ,30 han Boster Bi o-engineering min,carefully washedw ith distilled water,and Co, Ltd, ( China ) ; thenCyPA kit ( multiphase oligonucleotides probe and treatedw ith the imxture of 30% H Oand methanolhy-2 2 ( 1? 5) 0 for 30 imn, They were washedwith persensitive labeling technique was used to distilled synthe- water 3 ti mes before di gested with 3% pepsaseat size CyPA oligonucleotides probel abeled by 37 ? for 5, 120 s,and then washedwit h PBS for 5 digoxin min 3 times and distilled watero nce, Then they at 5') was bought from Wuhan BBoisoetnergi neering were Co, Ltd, ( China) ; and BX61 U pright optical fixed with paraformaldehyde at room temperatfure or mi- 10 min,and washedw ith distilled water 3 croscope was purchased O LfYMromPU S companyi nkept unwashed,wasHybridization solution ( 20 times, Af-L)μ added into each slice,which were coveredwi th dedi-Japan, ter tha,t20 of prehybridization solution was L μ 1, 1, 3 Processing of specimenscated coverli pss and hybridized at 37? overnight, add- The specimens in each group weredivi ded intoUncovered theli cses and theli sces were washedwi th ed,and thet issues were incubated at 37? for 4 ,h 4 part,s2 of which were fixed in 4% formalin,and2 ×SSC solution ( 37 ? ) for 5 min twice,and then Excess liquid waswi ped away,and thes lides were the other 2 were iputnto tubes and preservedin with 0, 2 × SSC o lsution ( 37 ? ) for 15 min once, Blocking reagent was added and ti sstuhe e liq-made into 4 m-thick The slices were under-μ slices,uwient d nir oturtoigenne, deparaffinating, hydration, and PBSslices 1ri, 2ns inMg, e tThheodns,they were putin to citrate buffer were incubated at 37 ? for 30 min, Excess 1so,l 2u,- 1 SP immunohistochemical stainingliquid The staining was conductedtr icstly following was discarded,and the lisdes were keptun washed,tion for natigen retrieval,and washedw ith PBS for the instruction of the SP immunohistochemical 3The tissue slices were incubated at 37? for 60 staining kit, The specimens were embedded in paraffin and times,3 min each time, Then onrmal goat serumwa smin dripped into the tissue slides to block for 20 after b iotinylated rat nati-digoxin was ddaed, andmin at room temperature, After the lobcking,rabbit washedw ith PBS for 4ti mes,5 min each, They were added with SABC,incubated at 37 ? for 20 min,anti- human CD147 or CyPanA ti body of working concen-and washedwi th PBS for 3ti mes,5 min each, Then velopment was performed and lithece s swere careful-1, 4 Statistical analysis ly washed w ith water, Then ehmatoxylin Data are presented as mean ? dsetviandard a- tion ( x ? ) s, T he s tatistical analyses were counter- processedstain,hydrochloric acid / alcohol differentiation by use of the tati sstical software were SPSS15, 0, Thedonef ollowed by routine washing,dehydration, comparison of CyPA and CD147exp ression level invitri- different groups was teswtiedth Kruskal Wallist fication,and slide covering, The result was test,observed and thec orrelation analysis of CyPA and CD147in with optical microscope,and the positive cells different body parts was tewsittedh Spearmans ’wereDouble-blind method that p2 eop leassess th e rhocstoaunitneidn,g rTehesu ltensg astiepvaer atceolntyr owlas i sppa pliroebde -firnee t his 2RESULTS study,method, P ， 0, 05 wasc onsidered as having hybrid- statisti-Staining of CD147 wdaset ermined as positive when ization solution,2, 1R esults of the SP immunohistochemical cal significance,yellow brown or bropwan rti cles presented in 1, 3 Criteria of judgestaining It was showed by immSPun ohistochemical stai- cell1, 3, 1 Immunohistochemical staining ning that,the expression of CyPA and CD147exi sted membran,eand thes taining of CyPA wase tedrmined in cells of then ormal skin froma ll the patients in as positive when ylelow brown or brown the 3 groups, CyPA wasm ainly distributed in the particles cyto- plasm,and CD147 existed mainly in the cell presentedin the cytoplasm, The staining results were mem- brane ( Fig, 1,2 ) , The IRIDI v alues of observedi n non-overlapping field of ivews of CyPA ex- pression in the skin from the shaded parts were optical 1, 35 ? 0, 49,2, 15 ? 0, 67,and 3, 55 ? 0, 76 in the microscope ( 10 × 40 gnmiafication ) , Five junior,middle age,and old age rgoup,respectively fields and the difference between the 3 groups had were picked out randomly in eachs lice,200 statisti- cal significance ( P ， 0, 05,Fig, 3 ) ; the IRIDI va l- ues of CD147 expression in the ksin cells from theh adsed parts were1, 20 ? 0, 41,2, 35 ? were countedin each ifeld,and the immunoreactivity 0, 67,and 3, 80 ? intensity distribution index ( IRIDI ) values of 1, 06 in the unjior,middle age,and old age rgoup, themarked with 0 , 3 poi nts IRIDI respectively and thed ifference between the gr3o ups cells were calculated, According to the assessment respectively, Thehad statistical significance ( P ， 0, 05, Fig, 3) , The IRI DI values of CyPAe xpression in the ofvalues were obtained by multiplying the 2, ,26,skin fromt he exposed parts wrere espec tively Bayramgurler,et al, ,the staining degreesw ere1, 3, 2 In-situ hybridizationDouble-blind method that p2 eop le assess th e 1, 40 ?0 , 50, classified into none,weak,medium,and strong,stain result separately was ppalied in this 2, 60 ? 0, 75,and 3, 80 ? 0, 89 in the junior,middle which were marked wit h 0 ,3 points respectively;study, The age,and old age grou,pand the idfference between the the r atio of positive cells were c lassified staining of CD147 and CyPA weaster mdined as posi-3 groups had statistical significance ( P ，0 , 05, into 0,Fig, 4) ; the IRIDIv alues of CD147e xpression in the tive when ylleow brown or bropwanr ticles presented skin from the exposed parts 1 , wer30 e ? 1% , 25% ,26% , 50% ,and ， 50% ,which were in the yctoplasm, The staining results were observed 0, 47, in non-overlapping field of ivews of optical 2, 75 ? 0, 79 and ,4 10 ?1 , 07 in the unjior,micro- middle age andol d age rgoup,respectively and the scope ( 10 × 40 gnmiafication ) , Five fi elds difference between the 3 groups tathaistdi cals significance ( P ， were 0, 05,Fig, 4) ,picked out randomly in eachs lide,200 cells The expression of CyPA and CD147 isnha dedwere parts wasp ositively correlated,and the countedi n eachf ield and the lvuaes of correlationexpression coefficient was 0, 899; the xepression of CyPA level were c alculated, The staining degrees andwere CD147 in exposed parts pwosasit ively classified into none, weak, medium and strong, correlated,which were marked wit h 0 ,3 points respectively; and the correlation coefficient was the ratios of positive cells were c lassified Fig, 1SP immunohistochemical staining showing the expression of CyPA and CD147 in the shadedn ormal skin ( × 400) ,A ,B, and C represented thepr eessxion of CyPA in the junior,middle age,and old age rgoup,respectively; D, E,and F represented thepr eessxion of CD147in the junior,middle age,and old age rgoup,respectively, Fig, 2SP immunohistochemical staining showing the expression of CyPA and CD147 in the exposedn ormal skin( × 400) ,A ,B, and C represented thepr eessxion of CyPA in the junior,middle age,and old age rgoup,respective- ly;D,E,and F represented thep reessxion of CD147in the junior,middle age,and old age rgoup,respectively, 6 * 6 * 5 5 e* 4 u l* Junior group e# au4 v# lJunior group 3 Middle agegroup av# # 3 Middle agegroup Old agegroup 2 Old age group 2 IRIDI 1 1 0 0 CyPA CD147 CyPA CD147 4 IRIDI values of CyPA and CD147 in the ex-Fig, Fig, 3IRIDI values of CyPA and CD147 in the shadedposed parts of each rgoup, Comparedw ith the parts of each rgoup, Compared wi th the junior junior group andi ddmle age grou,p* P ，0 , 05; group and middle age grou,p* P ，0 , 05; compared comparedwi th the junior group anodl d age rgoup, with the junior group anodl d age rgoup,#P ， 0, 05, #P ， 0, 05, IRIDI 1, 38 in the unjior,middle age,and old age rgoup,2, 2 Results of in-situ hybridization It was showed ibyn-s itu hybridization that and thed ifference between the 3 groups tahadtist is- the expression of CyPA and CD147exi sted in theK C cal significance ( P ，0 , 05,Fig, 7 ) , The of the normal skin from all the patients in the 3 groups,CyPA was many dstrbuted in the iliiaverage cytoplasm,and CD147 existed mainly in thenu cleus expresson eve vaues of CyPA e xpresson in illliand cytoplasm the ( Fig, 5,6) , The expression levels of CyPA expres- sion in the skin from shaded parts were skin from exposed parts rewserepect ively 1, 33 ? respectively 0, 71,2, 67 ? 1, 11,and 3, 67 ? 1, 25 in the 1, 67 ? 0, 75,2, 83 ? 1, 07,and 3, 83 ? 1, 67 in the junior, junior,middle age, and old age rgoup, and the difference between the 3 groups tahadtist icasl middle age and ol d age grou,pand the idfference sgnfcance ( P ， 0, 05,Fg, 7) ; the ii- iibetween the 3 groups tahad tisti casl expression level of CD147 expression in the ksin significance from shaded parwetrse respectively 1, 83 ? 1, 07,( P ， 0, 05,Fig, 8) ; the xepression level values 2, 67 ? 0, 94,and 3, 5 ? of CD147 expression in the skin from exposed par ts were respectively 1, 5 ?0 , 86,2, 69 ?1, 73,and 3, 63 ? 1, 46 in the unjior,middle age,and old age group,and the idfference between the 3 groupshad statistical significance ( P ， 0, 05,Fig, 8) , Fig, 5In-situ hybridization showing the expression of CyPA and CD147 mRNA in the shadedn ormal skin ( ×40 0) , A,B,and C represented thepr eessxion of CyPA in the junior,middle age,and old age rgoup,respectively;D,E, and F represented thepr eessxion of CD147in the junior,middle age,and old age rgoup,respectively, Fig, 6In-situ hybridization showing the expression of CyPA and CD147 mRNA in the exposedn ormal skin ( × 400) , A,B,and C represented thepr eessxion of CyPA in the junior,middle age,and old age rgoup,respectively; D,E, and F represented thepr eessxion of CD147in the junior,middle age,and old age rgoup,respectively, 6 6 * * * 5 * y5 t iysti4 n# # set# n4 # neitJunior group nni3 oiJunior group nMiddle agegroup 3 oiessMiddle agegroup rOld agegroup 2 pessrx2 pOld agegroup ExE1 1 0 0 CyPA CD147 CyPA CD147 Fig,8 mRNA expression levels of CyPA and CD147 in Fig, 7mRNA expession levels of CyPA and CD147 in rthe exposedp arts of each group, Comparedw ith the the shadedp as of each goup, Comparedw th the rtrijunior group andi ddmle age grou,p* P ， 0, 05; junior group and i ddmle age grou,p* P ， 0, 05; comparedwi th the junior group andol d age rgoup, comparedw th the junor group ando d age rgoup, iil #P ， 0, 05, #P ， 0, 05, The expression of CyPA and CD147 ishna dedThen,dose thei ncrease of CyPA e xpression in the parts waspo sitively correlated,and the process ofgi nag slow down or promote tgiheng apro- correlationgress? coefficient was 0, 792; the xepression of CyPA a ndIn somec hsolarsopinion,CyPA is a ’ CD147 in exposed parts pwoassi tively kind of ,17,correlated,antioxidant which plays an important roblode yin the dation-reduction regulation of be- humanoxi- and thec orrelation coefficient was 0, 782,cause CyPA cancom bine with various peroxidase to 3 DISCUSSION increase their activity,increase the ivability of The mechanism of ksin aging is very ocmplica-Cu / ted, So far,theories on ksin aging include free Zn superoxide dismutase ( SOD ) -1 mutated ,12,radi-cells,improve the cativity of SOD andG SH-Px, cal theor,ytheory of erhedity,telomere theory ndaand serves as the ROS scavengerrelie vet oox idative ,16,stress, CyPA cana ctivate the ERK1 /2 signalingso on, It is held by the freerad ical theory that,inpathway,increase the ivability of neuronsin the sthe process ofgi nga,ROS increase sand thec taivityit- of antioxidase decrease,sand that theacc umulateduation of oxidative stress andbl ood / oxygen- of damages caused xcbyess ieve ROS is them olecu-depriva- ,3234,-,27,tion,and protectc ells from oxidative damages,lar basis of gaing, The imbalance between theThe over-expression of CyPA incancer c ells can por- generation and elimination of ROS will leads to tect cells from paoptosis induced by oxidatiue oxi-stress ,28,dative stress,and thei rreversible throughi nhibiting ROS genenation and erlieving the depolarization of imtochondrial membranep otential,accumulation ,29,of damages causedRO byS is the key taogi ng,So,we deduces that toxheid ative stress ccaumulated CyPA is ah ighly conservedp rotein of 18k D,in the process ofki n sintrinsic aging and phwhich mainly exists in the yctoplasm and is otoaging may promote tgheene ration of CyP,Awhich startsex- pressedi n a wde range oft ssues, It has the the protectve functon of the body ando ws sdowniiiil ,35,actvtythe gang by nhbt the oxdatve stress, In iiiiiiii of peptdy proy cstrans somerase,whch addillli-iii- enabestion,CyPA can enhance theo prferaton of ebmryollii cerebral cells and various cancer cells,and t to promotpe ro ten fodng and transference,iili acti-inhibit ,3638,-vate isgnaling pathwa,yand ergulate the cativity apoptosis, So we deduced that CyPA a lmsayo oftake partin anti-aging activity by enhancing cell ,9,Varani J,WarnerR L,Gharaee-Kermani M,et al, Vitamin A The combined action of CD147 and CyPaA cti vates antagonizes decreaseced ll growth andl eevatde collagen-degrad- the ERK1 /2 signaling pathway,protects the neurons ,32-34,ing matrix metalloproteinases and stimulates collagen from oxidative damages,promote cell prolifera- accumula-,3638,- tion and inhibit apoptosis, Therefore,CD147 ton in naturay aged human k ns,J,, J Invest illiand CyPA arec osey reated,and the combned acllli- ,10, BaumannL , Skin ageing and its treatmnet,J,, J Pathol,Dermatol, tion of them can protcectell s from oxidative 2002000,7 11,214( 31 )( :2 48 ) 0: 48246,1 251 ,-- stress, ,11, Choi K J,Piao Y J,Lim M J,et al, Overexpressed promotece ll proliferation and inhibit cycophnlili apoptosis, The A in cancerc ells rendersre sistance to hypoxia and cisplatin--resut of our research showed thatpro tetnhe liin- and duced cell death,J,, Cancer Re,s2007,67( 8) : 3654-3662, mRNA of CD147 were expreissn edthe n ormal skin,12, Lee S ,PHwang Y S,Kim Y J,et al, Cyclophilin a binds to peroxiredoxins and activate sits peroxidase activity,J,, J of people of different ages, The expression level Biol in- Chem,2001,276( 32) : 29826-29832, creasedw ith the increase of age,and is ,13, Lee J 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