Fibroblast Growth Factors: A Controling Mechanism Of Skin Aging Part 2

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Growth Factors thiab tawv nqaij laus

Kev tshawb nrhiav cov tshuaj tshiab los tiv thaiv lossis txo cov txheej txheem kev laus tau dhau los ua qhov tseem ceeb hauv kev txhim kho cov cuab yeej tshuaj pleev ib ce tshiab, uas twb muaj ntau yam kev xaiv hauv kev siv, xws li antioxidants, retinoids, thiab alpha-hydroxy acids, anti-metalloproteinases ntawm silicon, thiab an-ti-glycans [26,27].

Rozman thiab Bolta [28] thiab Fitzpatrick thiab Rostan [29] pom tias cov tshuaj pleev ib ce ntawm kev loj hlob yam ua rau kev txhim kho cov duab cuam tshuam txog kev tsim cov collagen tshiab, epidermal thickening, thiab txhim kho kev kho mob ntawm daim tawv nqaij nrog pom kev txo qis ntawm wrinkles. Yog li, cov chav kawm ntawm kev loj hlob yam tseem ceeb tau ua rau muaj kev txaus siab ntawm cov tuam txhab cosmeceuticals raws li kev cog lus los tiv thaiv kev laus, vim cov kev tshawb fawb uas ntsuas lawv lub luag haujlwm kho hauv cov qhov txhab ntawm lub qhov txhab los ntawm kev txiav txim ntawm cov ntaub so ntswg rov tsim dua tshiab, uas pom tau tias muaj txiaj ntsig zoo rau cov tawv nqaij photoaging [30] , dhau los ua ib chav kawm dav tshawb fawb nyob rau hauv kaum xyoo dhau los ua cov tawv nqaij tiv thaiv kev laus.

Kev loj hlob yam tseem ceeb yog cov kev tswj hwm cov protein uas kho qhov teeb meem tseem ceeb ntawm txoj hauv kev thiab ua rau kev tsim kho ntawm tes thiab kho cov txheej txheem[30].cistanche qiaLawv ua ntawm qib cell membrane, ua kom muaj biochemical cascade uas txhawb cov kev hloov pauv ntawm cyclin-dependent kinases hauv cov cell nucleus, cov loj intracellular molecules uas tswj cov txheej txheem ntawm cell division.

Thov nias ntawm no kom paub ntxiv

Kev loj hlob yam tshwm sim feem ntau yog los ntawm kev khi rau tyrosine kinase receptors (Fig.1), uas ua rau autophosphorylation ntawm receptor thiab posterior phosphorylation ntawm serine, threonine, thiab tyrosine residues ntawm lub hom phiaj proteins xws li Raf-1, MAPK/Erk kinase(MEK) thiab-intracellular signal-regulated kinase-1(ERK)[13]. Cov enzymes no pib teeb liab cascades qhov twg txhua kinase activates ib qho hauv qab no los ntawm phosphorylation, inducing mitosis thiab cell faib thiab ua alterations nyob rau hauv cellular functions [31].

Cov Raf-1, MEK, thiab ERK cov proteins muaj nyob rau peb tsev neeg uas muaj npe sib txawv. ERK yog ib tug tswv cuab ntawm MAPK (mitogen-activated protein kinase) tsev neeg; MEK (extracellular signal-regulated kinase) yog ib feem ntawm MAPKK (mitogen-activated protein kinase) tsev neeg uas phosphorylates thiab activates ERK-MAPK. Raf-1 yog los ntawm tsev neeg ntawm MAPKKK (mitogen-activated protein kinase kinase) phosphorylase thiab activates MEK-MAPKK [32].

Yog li, los ntawm kev txhawb nqa kev loj hlob ntawm cov hlwb xws li fibroblasts thiab keratinocytes, kev loj hlob yam tseem ceeb ua lub luag haujlwm tseem ceeb hauv cov txheej txheem kho tawv nqaij, inducing reepithelialization los ntawm kev hloov cov txheej txheem ntawm collagen thiab elastin disorganized thiab reposition ntawm extracellular matrix nyob rau hauv cov laus daim tawv nqaij.

Kev siv cov khoom loj hlob yog ib qho tshiab los tiv thaiv kev laus kom rov zoo dua thiab thim rov qab cov cim ntawm daim tawv nqaij photoaged.cistanche tubulosa cov txiaj ntsig thiab kev phivKev nkag siab txog lub luag haujlwm ntawm kev loj hlob hauv kev kho qhov txhab tuaj yeem kwv yees lawv lub luag haujlwm hauv kev tsim kho ntawm daim tawv nqaij thiab rov ua kom tawv nqaij [33].

Fig.1.FGFs khi rau FGFRs, inducing receptor dimerization, kinase activation, thiab hloov pauv ntawm tyrosine residues los ntawm FGFR. Qhov no, nyob rau hauv lem, ua rau kom haum ntawm adapter proteins thiab qhov tshwm sim ua rau ntawm downstream signaling txoj kev. Lub tshuab ua kom FGFR2 substrate (FRS2) nrhiav thiab ua kom RAS-RAF-MAPK thiab PI3K-AKT txoj hauv kev koom nrog hauv kev loj hlob ntawm tes thiab kev ua haujlwm antiapoptotic, feem.cistanche tubulosa extractUa kom PKC thiab intracellular tso tawm ntawm Ca2 * yog induced los ntawm recruitment thiab phosphorylation ntawm PLCy, cov txheej xwm uas tswj cell motility.

Cistanche muaj kev tiv thaiv kev laus

FGF hauv Kev Tswj Ntawm Daim tawv nqaij laus

Cov neeg hauv tsev neeg FGF nce qhov kev loj hlob thiab kev ua kom cov fibroblasts los ntawm kev txhawb nqa cov khoom sib xyaw ntawm collagen nrog rau kev txhawb nqa endothelial cell division. Yog li, FGFs txhawb nqa angiogenesis, muaj lub luag haujlwm tseem ceeb hauv cov txheej txheem kho cell [6,13].

FGFs suav nrog cov pab pawg loj hlob ntawm cov qauv muaj feem cuam tshuam nrog polypeptide mitogens, uas suav nrog 23 qhov sib txawv me-bers.Ntxiv rau yav dhau los pom cov kua qaub FGF (aFGF, FGF-1) thiab FGF (bFGF, FGF-2) , tsev neeg kuj suav nrog int-2(FGF-3).proto-oncogene cov khoom (FGF-4), FGF-5, thiab FGF-6, thiab raws li keratinocyte kev loj hlob (KGF, FGF-7), androgen-induced growth factor (AIGF, FGF-8), GAF(FGF-9), thiab FGF-10, thiab lwm yam [34].

Nrog rau cov txheej txheem kev laus, fibroblasts muaj lawv cov haujlwm poob qis thiab yog li ntawd, cov synthesis thiab kev ua ntawm cov proteins uas lav elasticity thiab tsis kam xws li elastin thiab collagen kuj raug cuam tshuam. Yog li, nyob rau hauv cov laus cov tawv nqaij, muaj tsawg zus tau tej cov collagen los ntawm lub fibroblasts thiab ib tug ntau dua kev txiav txim ntawm cov enzymes uas degrade nws.cistanche tubulosa tshuaj xyuasQhov tsis muaj qhov sib npaug no ua rau cov txheej txheem kev laus [12,25].

FGF yog ib tsev neeg uas nthuav tawm ntau hom, ob qho uas sawv cev hauv cov txheej txheem ntawm tes taw qhia uas cuam tshuam nrog kev laus: fibroblastic acid kev loj hlob zoo (FGF) thiab cov txheej txheem fibroblastic loj hlob (FGF), uas cuam tshuam rau kev nrhiav neeg ua haujlwm, ua kom muaj zog, mitogenesis, tsiv teb tsaws, thiab sib txawv ntawm ntau hom cell. FGF thiab FGFb yog zais los ntawm ntau hom cell, xws li mast cells, endothelial cells, macrophages, thiab fibroblasts [35,36].

Feem ntau FGFs muaj qhov dav dav mitogenic spectrum thiab ua ntau yam dej num xws li txhawb kev loj hlob ntawm ntau yam mesodermal, ectodermal, thiab en-dodder mal cells thiab ua raws li neurotrophic thiab angiogenic yam hauv vivo[37]. Ib txoj kev tshawb fawb los ntawm Werner [34] tau qhia tias FGFa thiab FGFb txhawb nqa meso-, endo-, thiab ectodermal keeb kwm ntawm fibroblasts nrog rau kev loj hlob ntawm tes thiab kev sib txawv los ntawm lawv qhov kev ua mitogenic.

FGF receptors yog transmembrane tyrosine kinases nrog ob los yog peb lub immunoglobulin zoo li domains thiab ib cheeb tsam acidic heev nyob rau hauv lub extracellular feem. FGFs khi rau tyrosine kinase receptors ua rau nws dimerization thiab pib lub teeb liab intracellular transduction cascade [38].cistanche UKCov tswv cuab sib txawv ntawm FGF tsev neeg tuaj yeem khi rau plaub qhov sib txawv paub FGF receptors (FGFR1-FGFR4) nrog rau kev sib txawv, thiab tuaj yeem ua raws li kev sib txuas, ua rau muaj ntau yam tshwm sim xws li kev loj hlob [39], kev sib txawv, Kev tsiv teb tsaws, ciaj sia, kev faib cell thiab kev loj hlob [40], thiab kho qhov txhab [41].

Txawm hais tias lub luag haujlwm ntawm FGFs yog tus cwj pwm zoo, lawv cov txheej txheem ntawm kev ua haujlwm tseem tsis tau meej meej. Nws paub tias nws cuam tshuam nrog kev sib cuam tshuam ntawm cov xov tooj ntawm tes uas yuav cuam tshuam nrog RAS-MAP kinases txoj hauv kev, PI3K-AKT, PLC-y, lossis STAT. Yog li ntawd, FGF cell signaling muaj kev cuam tshuam nrog ntau lub xov tooj ntawm tes taw qhia txoj hauv kev thiab cov tswv yim nyuaj [42].

Phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K-AKT) yog cov enzymes uas ua haujlwm ntawm ntau theem ntawm cov teeb liab intracellular transduction. PI3K / Akt-mediated signal transduction tej zaum yuav pib los ntawm kev cuam tshuam nrog receptor tyrosine kinases los yog los ntawm kev khi nrog cov G protein me me, Ras[43].Yuav ua li no, lawv nthuav tawm cov haujlwm hauv kev tswj kev loj hlob, tsiv teb tsaws, ciaj sia, thiab cellular metabolism. , nrog rau hauv cov noob qhia, calcium flux, inflammatory teb, thiab cytoskeletal rearrangements [44].

Phospholipase C- (PLC-y) yog ib qho isoform ntawm PLC tsev neeg thiab nws qhov kev ua haujlwm tau tsim los ntawm ob yam khoom: inositol 1,4, 5-triphosphate thiab diacylglycerol (DAG). Thawj qhov ua rau muaj kev hloov pauv hauv cytosolic dawb Ca2 ntxiv rau qhov concentration (Ca2 ntxiv ) yog qhov tseem ceeb rau cov lus teb ntawm cov neeg ua haujlwm xws li kev loj hlob, vim nws yog lub luag haujlwm rau kev ua kom cov protein kinase C isoforms; Kev tsim ntawm inositol nyob rau hauv lem yog cuam tshuam nrog kev nce ntxiv hauv intracellular dawb Ca2 ntxiv [45]. Cov qub ua rau muaj kev nce ntxiv hauv intracellular dawb Ca2 ntxiv, thaum lub sijhawm tom kawg ua haujlwm ncaj qha ntawm ntau cov protein kinase C isoforms thiab yog li tseem ceeb rau cov lus teb ntawm cov neeg ua haujlwm xws li kev loj hlob.

Cov kev hloov pauv hauv tsev neeg ntawm cov teeb liab transducers thiab transcription activators (STAT) muaj feem xyuam rau ntau yam cytokine signaling pathways, tshwj xeeb tshaj yog cov uas qhib lub gp130 membrane receptor. Los ntawm JAK-STAT (Janus-tsev neeg tyrosine kinase / signal transducer thiab activator of transcription) qhia txoj hauv kev, ntau yam cytokines thiab kev loj hlob yam ua rau lawv cov teebmeem lom. STATs tsim homo-thiab heterodimers thaum phosphorylated, uas tso cai rau lawv nkag mus rau hauv lub nucleus, uas lawv tuaj yeem tswj hwm cov noob hloov pauv [46].

Cov tshuaj formulations uas muaj kev loj hlob yam xws li FGF tau dhau los ua ib qho kev xaiv dermo-cos-metic rau cov khoom siv los tiv thaiv kev laus, vim tias theem ntawm kev loj hlob tuaj yeem txo qis nrog kev loj hlob ntawm lub hnub nyoog, thiab cov no, nyob rau hauv lem, muaj lub luag haujlwm tseem ceeb hauv kev loj hlob. kho ntawm extracellular matrix [4,13,20].

FGFs cuam tshuam rau Cov Txheej Txheem Kev Laus

Acid Fibroblastic Growth Factor (FGF-1, FGFa) Kev ua kom FGFs txhawb cov teebmeem uas pab ua kom muaj kev laus qeeb. Ua kom FGF-1 txhim kho daim tawv nqaij elasticity thiab induces lub synthesis ntawm collagen thiab elastin[4,13,47].Xie li al.[48] siv FGFatorat ulcers thiab soj ntsuam cov proliferation thiab migration ntawm epithelial hlwb thiab fibroblast augmentation.

FGF-1 belongs rau tsev neeg loj ntawm kev loj hlob yam tseem ceeb uas khi rau transmembrane receptors nrog cytoplasmic tyrosine kinase domain. FGF-1 yog ib qho mitogen muaj zog koom nrog hauv kev txhawb nqa ntawm kev sib txuas thiab kev loj hlob ntawm DNA los ntawm ntau hom cell, nrog rau cov hlwb mast, endothelial hlwb, macrophages, thiab fibroblasts. Nws ua lub luag haujlwm tseem ceeb hauv ntau theem ntawm kev loj hlob thiab morphogenesis, nrog rau hauv cov txheej txheem angiogenesis thiab kho qhov txhab [24]. Yog li ntawd, vim nws txoj haujlwm mitogenic, FGF-1 tau dhau los ua cov khoom muaj peev xwm muaj peev xwm nrog ntau yam kev siv hauv cosmetology qhia rau ntau yam txheej txheem ntawm daim tawv nqaij, txhawb nqa meso-, endo-, thiab ectodermal hlwb, suav nrog fibroblasts, keratinocytes, macrophages, thiab endothelial hlwb.

Ib txoj kev tshawb fawb tau tshawb xyuas qhov cuam tshuam ntawm FGF-1 rau ntawm daim tawv nqaij thiab tshuaj xyuas cov khoom tiv thaiv kev laus ntawm kev hloov kho caj ces FGF-1 los txhim kho nws txoj kev ruaj ntseg thiab tiv thaiv kev puas tsuaj rau protease (Q40P/S47I/H93Grecom-Dinant FGF -1 [rFGF) ua tus neeg sawv cev hauv cov tshuaj pleev ib ce [33]. Cov txiaj ntsig tau pom tias FGF-1 muaj txiaj ntsig zoo rau kev loj hlob ntawm tes ntawm keratinocytes thiab fibroblasts, uas tau lees paub los ntawm txhua qhov kev sim (hauv vitro, ex vivo, thiab hauv vivo) nrog Q40P/S47I/H93GrFGF{{13} }, qhia txog lub peev xwm loj rau kev siv cov protein no hauv cov khoom siv tawv nqaij los tiv thaiv kev laus thiab kho qhov txhab.

Cov txiaj ntsig zoo kuj tau txais hauv txoj kev tshawb fawb los ntawm Ha thiab cov npoj yaig [49], uas tau tsim ib qho kev nthuav qhia uas muaj peev xwm ua tau rau tib neeg recombinant aFGF(RH-FGF1) us-ing transient thiab DNA replicon vector qhia hauv Nicotiana benthamiana. Txoj kev tshawb no tau soj ntsuam cov txiaj ntsig ntawm kev loj hlob yam ntawm UVB-induced daim tawv nqaij photoaging. Cov txiaj ntsig ntawm txoj kev tshawb fawb no tau pom tias rh-FGF1 tsis yog tsuas yog nce cell viability tab sis kuj cell proliferation. Kev kho mob kuj tau pom tias muaj kev tiv thaiv tseem ceeb tiv thaiv UVB-induced cytotoxicity, ntxiv rau kev rov ua kom rov qab tau cov nyiaj procollagen ploj los ntawm hluav taws xob. Yog li, rh-FGF1 tau pom tias muaj txiaj ntsig zoo rau kev tiv thaiv UVB-induced oxidative teebmeem rau ntawm daim tawv nqaij, muaj peev xwm ua kom zoo nkauj thiab kho tus neeg sawv cev uas tuaj yeem siv los tiv thaiv kev laus.

Basic Fibroblastic Growth Factor(FGF-2,bFGF) Basic FGF(FGF-2) txo thiab tiv thaiv cov kab thiab wrinkles los ntawm kev ua kom cov tawv nqaij tshiab thiab txhawb kev loj hlob ntawm cov hlwb mesodermal, ectodermal, thiab endodermal keeb kwm, feem ntau yog fibroblasts thiab keratinocytes. Tag nrho cov no qhia tias FGF-2 tuaj yeem yog qhov tseem ceeb hauv kev hloov pauv ntawm cov txheej txheem ib txwm muaj xws li angiogenesis, kho qhov txhab, thiab kho cov ntaub so ntswg, nrog rau kev tiv thaiv kev laus[4,13,47]. Txhawm rau txhim kho nws cov kev ua, FGF-2 khi rau high-affinity tyrosine kinase receptors, uas nws ua kom ua rau receptor autophosphorylation thiab phosphorylation ntawm lwm cov substrates, uas tuaj yeem txhawb nqa cov haujlwm ntawm tes xws li kev loj hlob, kev txav mus los, thiab kev sib txawv [50].

Txhawm rau tiv thaiv FGF-2 los ntawm thermal proteolysis hauv daim tawv nqaij laus thiab khaws nws cov txiaj ntsig zoo ntawm kev loj hlob ntawm fibroblasts, kev tshawb fawb tau soj ntsuam cov haujlwm ntawm Hibiscus Abelmoschus noob extract ua cov khoom tiv thaiv [51]. Cov txiaj ntsig tau pom tias cov extract tau nthuav tawm cov tshuaj tiv thaiv kev tiv thaiv ntawm FGF-2, uas tso cai rau kev txhawb nqa ntawm tes hloov pauv los ntawm qhov xwm txheej no. Nyob rau hauv tib txoj kev tshawb no, Rival et al.[51] soj ntsuam nyob rau hauv 60 noj qab haus huv tib neeg tuaj yeem pab dawb los tiv thaiv kev laus ntawm cov extract, nyob rau hauv ib tug ob-dig muag placebo-tswj kev soj ntsuam kev tshawb fawb. Kev txhim kho tseem ceeb hauv wrinkles, kev ntxhib los mos, elasticity thiab ntom ntawm daim tawv nqaij tau pom, tsawg kawg yog ib feem, vim heparan sulfate zoo li cov nroj tsuag no thiab tiv thaiv FGF-2 los ntawm thermal degradation. Hauv kev xaus, H. Abelmoschus noob extract tau qhia txog kev tiv thaiv kev laus los ntawm kev tiv thaiv FGF-2 cov ntsiab lus tam sim no hauv tib neeg cov tawv nqaij, kom nws muaj peev xwm tswj tau nws cov haujlwm ntau hauv kev pom zoo ntawm daim tawv nqaij rejuvenation.

Nyob rau hauv xyoo tas los no, cov tshuaj pleev ib ce thiab txhaj tshuaj loj hlob tau tshwm sim raws li kev kho mob zoo nkauj uas tuaj yeem siv tau rau kev kho kom zoo nkauj thiab kho mob. Ib pawg ntawm cov kws tshawb fawb, uas kuj tau kawm FGFs, tsom mus rau kev soj ntsuam ib txoj hauv kev vivo rau kev laus ntawm daim tawv nqaij rejuvenation los ntawm kev txhaj tshuaj ncaj qha ntawm intradermal FGF-2[52]. Cov teebmeem hauv qab no tau pom zoo: kev txhim kho ntawm daim tawv nqaij smoothness, atrophied ntawm daim tawv nqaij tuab, thiab txhim kho viscoelasticity. Cov kev hloov pauv hauv viscoelasticity ua ntej thiab tom qab kev kho mob tau muab piv rau lub hnub nyoog sib txawv ntawm ntau tshaj 20 xyoo.

Keratinocyte Growth Factor (FGF-7, KGF)

Qee cov khoom siv los tiv thaiv kev laus uas muaj cov khoom loj hlob tau raug tsim tawm. Ib qho piv txwv yog keratinocyte kev loj hlob zoo (KGF), uas yog ib tug tswv cuab ntawm tsev neeg FGF. Thaum FGFs feem ntau cuam tshuam rau kev loj hlob thiab / lossis kev sib txawv ntawm ntau hom cell, KGF zoo li ua tshwj xeeb rau cov hlwb epithelial [34].

Ib txoj kev tshawb nrhiav tsom mus rau kev tshawb fawb txog kev ua tau zoo, kev ua siab ntev, thiab kev siv cov khoom lag luam uas muaj cycloartenol (ib qho purified extract), antioxidant peptides, thiab siab concentrations ntawm peb txoj kev loj hlob: transforming kev loj hlob factor-beta 1, epidermal kev loj hlob factor, thiab KGF. Lub peev xwm los txo qhov pom cov cim ntawm kev laus, suav nrog cov kab zoo thiab wrinkles, kev ntxhib los mos, pore loj, elasticity, liab, hydration, thiab tag nrho cov tawv nqaij zoo, tau soj ntsuam, los ntawm kev soj ntsuam ntawm pom cov cim hauv cov duab. Cov txiaj ntsig tau pom tias kaum yim ntawm nees nkaum qhov kev kawm tau ntsib kev txhim kho tseem ceeb tom qab tsuas yog 2 lub lis piam ntawm kev siv rau txhua pawg ntsuas thiab 100 feem pua ​​​​ntawm cov kev kawm tau pom tias muaj kev txhim kho tsawg kawg 3 lossis ntau dua ntawm 8 pawg raws li kev soj ntsuam, xaus lus tias cov khoom siv tau zoo. rau cov tib neeg uas nrhiav kev txhim kho tseem ceeb ntawm daim tawv nqaij laus [53].

FGFs thiab daim ntawv thov kom zoo nkauj

Raws li cov ntaub ntawv pov thawj hais txog kev tiv thaiv kev laus ntawm daim tawv nqaij los ntawm kev loj hlob, cov khoom muag tshuaj-logical uas muaj ntau hom FGFs tau txheeb xyuas thiab lawv tau teev nyob rau hauv Table 1.

Xaus

Kev siv cov khoom loj hlob tau txais cov khoom lag luam hauv cov tshuaj pleev ib ce raws li kev xaiv kho tshiab los tiv thaiv thiab tswj cov txheej txheem kev laus, vim nws cov kev ua hauv cellular.

txheej txheem sib txawv. FGF plays lub luag haujlwm tseem ceeb hauv kev tiv thaiv kev laus vim tias nws muaj feem cuam tshuam rau kev cuam tshuam ntawm collagen thiab elastin synthesis lub luag haujlwm rau cov tawv nqaij elasticity thiab tsis kam, cov yam ntxwv uas ploj zuj zus nrog cov tawv nqaij laus, ob qho tib si sab hauv thiab sab hauv. Txawm li cas los xij, kev tshawb fawb ntxiv yog xav tau kom nkag siab tag nrho cov txheej txheem ntawm kev ua ntawm kev loj hlob, tshwj xeeb tshaj yog FGF. Kev nkag siab zoo ntawm cov tshuaj no ua haujlwm li cas yuav tso cai rau kev txhim kho cov khoom lag luam zoo dua thiab muaj kev nyab xeeb dua nrog lub hom phiaj zoo nkauj.

Kab lus no tau muab rho tawm los ntawm Darízy Flávia Silva, PhD Lub Tsev Haujlwm Saib Xyuas Kev Noj Qab Haus Huv Kev Noj Qab Haus Huv, Department of Bioregulation Federal University of Bahia, Avenida Reitor Miguel Calmon S/N, Salvador, Bahia 40110-902 (Brazil) E-Mail darizy.silva@ufba.br