Kakaretso
Thymosin beta 4 (TV4) ke protheine e nyenyane ea molek'hule e entsoeng ka masala a mangata a amino acid 'me e ajoa ka bongata liseleng tse fapaneng tsa' mele oa motho..[1][2] E le e 'ngoe ea limolek'hule tse laolang actin' meleng oa motho, e na le mesebetsi e mengata ea likokoana-hloko 'me e phetha karolo ea bohlokoa tsosolosong ea lisele, nchafatso, pholiso ea maqeba, ho boloka tekanyo ea actin, ntshetsopele ya hlahala le metastasis, apoptosis ea lisele, ho ruruha, angiogenesis, ntshetsopele ya follicle ya moriri, le mekhoa e meng ea fisioloji le ea mafu.
Mesebetsi ea Likokoana-hloko le Mekhoa ea Ts'ebetso
Tβ4 ke e 'ngoe ea limolek'hule tsa mantlha tse laolang actin 'meleng oa motho ebile e na le mesebetsi e mengata ea tlhaho, e bapala karolo ea bohlokoa ho nchafatseng lisele, nchafatso, pholiso ea maqeba, ho boloka tekanyo ea actin, ntshetsopele ya hlahala le metastasis, apoptosis ea lisele, ho ruruha, angiogenesis, ntshetsopele ya follicle ya moriri, le mekhoa e meng ea fisioloji le ea mafu.
Mohloli: Mohala oa mohala oa meno
- Ntho e laolang actin: Actin e nka hoo e ka bang 10% ea kakaretso ea protheine liseleng tseo e seng tsa mesifa 'me ke karolo ea bohlokoa e hlokahalang bakeng sa sebopeho sa lisele, motsamao wa sele, le ho fola maqeba. Ho ba teng ha Tβ4 ka liseleng ho lekane ho arola li-monomer tsohle tsa actin le ho kenya letsoho ho laola actin polymerization le depolymerization.. Tβ4 e ka tlama ho actin monomers ka 1:1 karolelano, ho thibela ho thehoa ha li-polymers tsa F-actin. Ho tlama ha Tβ4 ho actin ho tsamaisana le ho arohana ha metsi a tlamiloeng. C-terminal ea Tβ4 e tlama ho sebetsa His-40, ho baka phetoho e tshoanang le ho actin monomers. Molek'hule ea Tβ4 e na le sebaka se tlamang actin (TSIETSOE), e leng sebaka se seholo sa ho ikopanya le electrostatic. Sekhechana sa eona sa N-terminal se ka thibela polymerization ea actin ka tšitiso ea steric. Ha o sebetsa o le mong, Tβ4 e ka thibela actin polymerization le phapanyetsano ea nucleotide ho actin. Sena se fapane le karolo ea protheine e 'ngoe e tlamang actin, Profile, e khothalletsang phapanyetsano ea ADP le ATP, ho potlakisa kopano ea actin. [1][2]Tβ4 le Profilin li ka laola kopano ea actin ka tumellano. Tβ4 e ka laola phetoho lipakeng tsa G-actin le F-actin. Ho tlalehiloe hore khatello ea Tβ4 e fihla 300 pmol liseleng tsa mali tse tsamaeang haholo, athe mahloriso a hlokahalang bakeng sa Tβ4 ho tlamahane le G-actin a le ka tlase ho 20 pmol. Ka ho eketseha ha mahloriso, Tβ4 e fokotsa matla a depolymerization a F-actin. Sena e ka 'na ea e-ba lebaka leo ka lona Tβ4 e laolang mosebetsi oa tsamaiso ea microfilament ea cellular.
Khothatso ea endothelial cell migration le angiogenesis: Lithuto tse sebelisang lera la khoho la chorioallantoic (CAM) angiogenesis model e bonts'itse hore ha lisele tsa endothelial li arohana ka likarolo tsa tubular, litaba tsa mRNA tsa Tβ4 li eketseha ka makhetlo a mahlano, 'me phetisetso ka Tβ4 e potlakisa ho thehoa ha li-tube-like structures ka endothelial cell clones.. Ho phaella moo, lipatlisiso li fumane hore Tβ4 e ka sebelisana le fibrin le collagen e kopanetsoeng ke transglutaminase (Ntlha ea XIIIa) le ho phetha karolo ea bohlokoa ts'ebetsong ea ho thibela mali. Ho feta moo, tekong ea ho lemala ha letlalo la botenya bo felletseng ho litoeba tse tsofetseng tsa lefu la tsoekere, Tβ4 e ka potlakisa ho fola ha maqeba a letlalo a sebaka se seholo le ho chesa ho tebileng, khothalletsa ho lokisa letlalo le cornea, le ho bontša bokhoni ba ho potlakisa pholiso ea maqeba.
Thibelo ea apoptosis ea lisele: Tβ4 e na le ts'ireletso e kholo liseleng tsa corneal epithelial tse senyehileng ke lintho tse senyang joalo ka benzalkonium chloride kapa ethanol.. Ho phahama ha polelo ea liphatsa tsa lefutso tsa Tβ4 ho molemo bakeng sa ho matlafatsa hypoxia ea lisele.[2][3]
Ho fokotseha ha limolek'hule tsa bohlokoa tsa ho ruruha: Pholiso ea maqeba ke mokhoa o rarahaneng oa likokoana-hloko o ka aroloa ka mekhahlelo e meraro e fapaneng: ho ruruha, ho ata ha lisele, le ho nchafatsa lisele, ka polelo ea liphatsa tsa lefutso tsa liprotheine tse amehang li ntse li laoloa ebe li theoleloa mohatong ka mong. Bakeng sa maqeba a sa foleng, ts'ebetso ena ea taolo e ka sitisoa ke lintlha tse kang lilemo, mafu a teng, le lithethefatsi tsa immunosuppressive, ho lebisa tlhahisong e feteletseng ea limolek'hule tsa ho ruruha, ho ruruha ho feteletseng, le ho sitisa ho ata ha lisele le ho nchafatsa lisele. Lipatlisiso li fumane hore Tβ4 e ka fokotsa maemo a li-radicals tsa mahala, fokotsa lipid peroxidation, thibela tlhahiso ea li-cytokine tsa ho ruruha tse kang IL-1, macrophage inflammatory protheine 1α (MIP1a), MIP1β, monocyte chemotactic protheine-1 (MCP-1), fokotsa maemo a thromboxane le prostaglandin 2a, ka hona ho kokobetsa ho ruruha. Ka hona, e ka sebelisoa bakeng sa ho phekola mafu a ho ruruha a kang segmental enteritis le atrophy ea mesifa.
Ho tsosoa ha phapang ea lisele tsa batho ba baholo ba epicardial stem: Tβ4 e bapala karolo ea bohlokoa likarolong tse fapaneng tsa nts'etsopele ea likepe tsa coronary 'me e ka susumetsa kholo ea li-gfts tsa epicardial tse khutsitseng., ho tsosolosa multipotency ea fibroblasts, lisele tse boreleli tsa mesifa, le lisele tsa endothelial, le ho susumetsa phapang ea bona.[1][2] Ho phatloha ha mofuta oa Tβ4 ka pelong ho lebisa phokotseho e kholo maemong a sehlahisoa sa angiogenic cleavage sa Tβ4. (AcSDKP). Leha ente ea AcSDKP e sa khone ho khutlisa pelo, e ka ntlafatsa haholo phapang ea lisele tsa batho ba baholo ba mouse epicardial ho lisele tsa endothelial. Sena se fana ka maikutlo a hore Tβ4 le AcSDKP ke li-stimulators tse matla tsa pelo le methapo ea methapo, 'me lisele tsa epicardial tse entsoeng ke batho ba baholo ba Tβ4 li ka sebetsa e le mohloli oa tsosoloso ea methapo, e lebisang ho tsosolosoa ho tsitsitseng ha vasculature e senyehileng boemong bo tlaase ka mor'a kotsi ea pelo.
Khothatso ea nts'etsopele ea follicle ea moriri: Tβ4 e khothalletsa ho falla, karohano, le ho tsosolosoa ha matrix ea extracellular ea lisele tsa stem tsa moriri, ka hona ho laola kholo ea moriri. Lithuto tsa likhoto le litoeba li fumane hore nakong ea potoloho ea kholo ea moriri, karolo e itseng ea follicle ea moriri keratinocyte e tsoang sebakeng sa bulge haholo-express Tβ4, ha lisele tsa stem tsa letlalo li boetse li le teng ka har'a leqhubu la moriri. Ha khatello ea Tβ4 e le boemong ba nanomolar, ho falla le ho arohana ha lisele tsa stem ho ntlafatsoa, 'me boteng ba Tβ4 bo boetse bo eketsa polelo le secretion ea matrix metalloproteinase-2 (MMP-2), enzyme ea extracellular e senyang matrix.
Kamano le ho thehoa ha hlahala: Ho phahama ha mofuta oa Tβ4 ho 'nile ha bonoa liseleng tse sa tšoaneng tsa hlahala, ho akarelletsa le medullary thyroid carcinoma, kankere ea mala, melanoma e kotsi haholo, kankere ea matsoele, le oral squamous cell carcinoma. Tβ4 e ka susumetsa ka nepo polelo ea vascular endothelial growth factor, ho khothaletsa angiogenesis le ho kenya tšebetsong thepa ea ho falla ha lisele, ho lebisa ho lefu la hlahala. Ho phahama ha polelo ea Tβ4 ho fella ka ho fokotseha ha polelo ea E-cadherin, ho fokolisa ho khomarela lisele, le polelo e eketsehileng ea matrix metalloproteinase, ho fana ka monyetla oa kholo le litšobotsi tse hlaselang lisele tsa mofetše, ka hona e tlatsetsa ho mpeng. Tβ4 e na le matla a anti-apoptotic, le polelo e ntseng e eketseha ea Tβ4 e ka fokotsa boholo ba apoptosis ea lisele, mohlomong ka lebaka la Tβ4 e thibelang ho lokolloa ha cytochrome c le ho sitisa ho qalisoa ha mokhoa oa apoptosis, e leng tšobotsi e 'ngoe ea bohlokoa ea lihlahala tse kotsi.
Khothatso ea tokiso ea cornea: Thymosin β4 e bonts'itse bokhoni ba eona ba ho khothaletsa pholiso ea maqeba mefuteng e fapaneng ea likotsi tsa cornea le ho laola tlhahiso ea li-cytokine tse itseng tsa bohlokoa.. Lipatlisiso li fumane hore thymosin β4 e ka fokotsa polelo ea matrix metalloproteinase, ho khothaletsa ntlafatso ea matrix ea extracellular, le ho kenya tšebetsong li-cytokine. Ka ho toba, e thibela mosebetsi oa matrix metalloproteinases, ho fapana le qeto e nkiloeng ho mefuta ea kotsi ea letlalo ea thymosin β4. [1][2][3]Sena se fana ka maikutlo a hore litsela tsa taolo tsa li-enzyme tse itseng tšebetsong ea tokiso ea lisele li ka fokotsoa kapa tsa fokotsoa..
Mokhoa oa ho itokisa
Hajoale, ho na le mehloli e 'meli e meholo ea thymosin beta 4 (TV4) e sebelisoa litsing tsa kliniki le tsa lipatlisiso: ho ntšoa ho tsoa ho thymus ea bovine le motsoako oa lik'hemik'hale. Ho ntša Tβ4 ho tswa ho bovine thymus ha ho theko e boima feela empa hape ho fokotsoa ke ho fumaneha ha thepa le mekhoa ea ho ntša., se bakang bohloeki bo tlase le dikahare tse tlase. Ho ba teng ha litšila le hona ho tlisa litaba tse ngata, haholo-holo ha ho nahanoa ka palo e ntseng e eketseha ea likokoana-hloko likhomong, e thatafatsang mosebetsi wa ho ntsha. Ka nts'etsopele ea boenjiniere ba liphatsa tsa lefutso, ho sebelisa mekhoa ea boenjiniere ba liphatsa tsa lefutso ho hlahisa Tβ4 e tla fetoha tataiso e ncha. Ka laboratoring ea rona, re rera ho etsa polelo ea tandem ea Tβ4 e entsoeng ka maiketsetso limeleng ho fumana limela tsa transgenic tse nang le polelo e nepahetseng ea Tβ4.. Ha ho bapisoa le Tβ4 e nkiloeng ka tlhaho, Tβ4 e hlahisoang ka ho sebelisa limela tsa transgenic e na le melemo ea bioactivity e phahameng, bohloeki bo phahameng, le litla-morao tse fokolang. Ho phaella moo, e emela mokhoa o nepahetseng oa ho fokotsa litšenyehelo tsa tlhahiso, ho fokotsa tshilafatso, le ho etsa hore tlhahiso e kholo.[3]
Ka morao
Thymosin beta 4 ke peptide e entsoeng ka 43 masalla a amino acid a nang le ntlha ea isoelectric ea 5.1 mme e baballwa haholo ho diamusi. Ke protheine ea cytoplasmic ho fapana le protheine ea nyutlelie, ho fapana le thymosin alpha kapa thymosin tse tšoanang. [2][3]Thymosin beta 4 e ameha mesebetsing e fapaneng ea 'mele, ho kenyeletsa ts'ebetso ea 'mele ea ho itšireletsa mafung, ntshetsopele ya tsamaiso ya methapo, pholiso ea maqeba, le mesebetsi ea protheine ea actin.
Ho fapana le thymosin alpha kapa thymosin tse tšoanang, thymosin beta 4 ke protheine ea cytoplasmic ho fapana le protheine ea nyutlelie. E na le li-amino acid tse fokolang tsa hydrophobic mme ha e na sebaka sa sebopeho sa Lys-Lys-Xaa-Lys.. Lithuto tsa conformation tsa lik'hemik'hale li bontšitse hore thymosin beta 4 e teng mme e sebetsa joalo ka ketane e le 'ngoe. E na le sebaka sa ho pheta-pheta ka hare pakeng tsa mesaletsa 31-43 le 18-30, e nang le li-amino acid tse tšeletseng tse tšoanang. Le hoja ho na le libaka tse peli tsa helical haholo pakeng tsa masala 4-12 le 32-40, thymosin beta 4 ha e etse phetoho ea proline. Mabapi le kabo ea baeloji le polelo, thymosin beta 4 e ile ea hloekisoa qalong ho tloha ho thymus. Ka hona, qalong ho ne ho lumeloa hore ke hormone ea thymic e sebetsang ka nako ea pele ea T-cell maturation. Leha ho le joalo, thymosin beta 4 e teng haholo liseleng tse ling, litho tsa mmele, le lisele, e nang le maemo a phahameng ka ho fetisisa a tholahalang lesapong, thymus, matšoafo, le macrophages ea peritoneal, e lateloe ke boko, sebete, liphio, testes, le pelo. Esita le lisele tsa tsamaiso ea non-reticuloendothelial tse kang fibroblasts li ka kopanya thymosin beta. 4. Li-thymocyte li na le maemo a phahameng ka makhetlo a supileng a thymosin beta 4 mRNA ho feta lisele tsa thymic stromal, le thymosin beta 4 polelo e bonoa ka mefuta e fapaneng ea lisele tsa mali. Boithuto ka thymosin beta 4 cDNA e bontšitse hore ha e na peptide ea matšoao.[1] Leha ho boetse ho na le liprotheine tse patiloeng 'meleng tse haelloang ke li-peptide tsa matšoao, joalo ka interleukin-1 (IL-1) le lintlha tsa kholo ea endothelial, litsebi li ntse li lumela hore thymosin beta 4 ha ho bonolo hore e be protheine e patiloeng 'me ho ka etsahala hore e be ea bohlokoa bakeng sa mesebetsi e itseng ea motheo ea lisele.
Kopo
Patlisiso ea mantlha le e sebelisitsoeng mabapi le ho Ntlafatsa Ts'ebetso ea Endothelial Progenitor Cell ka Thymosin Beta. 4 (TV4)
Sekhahla le sekhahla sa lefu la mafu a pelo ea ischemic se ntse se eketseha selemo le selemo, ho beha kotsi e tebileng bophelong ba batho. Pathogenesis ea mafu ana e rarahane haholo, le ho se sebetse ha lisele tsa endothelial ho phetha karolo ea bohlokoa ho nts'etsopele ea mafu a pelo ea ischemic.. Le hoja lisele tsa endothelial tse hōlileng tsebong li ka lokisa tšenyo ea endothelial, matla a bona a ho tsosolosa a lekanyelitsoe. Lisele tsa endothelial progenitor (Li-EPC) ke mofuta oa sele e tlang pele bakeng sa lisele tsa vascular endothelial mme e na le monyetla oa ho ikarola ka lisele tsa endothelial.. Liphuputso tse ngata li bonts'itse hore li-EPC li bapala likarolo tse fapaneng ho lokisoeng ha methapo ea mali le neovascularization. Leha ho le joalo, ts'ebeliso ea bongaka ea phetisetso ea EPC e ntse e tobana le mathata a mangata. Mafu a 'maloa a pelo le methapo kapa mabaka a kotsi joalo ka botsofali, khatello ea mali, hypercholesterolemia, 'me lefu la tsoekere le ka fokotsa palo ea li-EPC tse potolohang le ho senya mosebetsi oa tsona, e fokotsa haholo ts'ebeliso ea bona ho mafu a pelo ea ischemic. Ka hona, ho ntlafatsa mosebetsi oa li-EPC e tla ba leano la bohlokoa bakeng sa phekolo ea phetisetso ea EPC nakong e tlang.[1][2]
Thymosin beta 4 (TV4), protheine e boima bo tlase ba molek'hule e entsoeng ka 43 masalla a amino acid, e ameha ho tsamaelaneng le likarabelo tse fapaneng tsa baeloji joalo ka angiogenesis, pholiso ea maqeba, le taolo ea ho ruruha. Patlisiso ea rona e fetileng e fumane hore Tβ4 e ka ntlafatsa ho ata le ho falla ha li-EPC tsa mali tsa motho ha li ntse li thibela apoptosis le senescence ea tsona.. Tβ4 e eketsa haholo bokhoni ba angiogenic ba EPCs, e bontshang kamano e itshetlehileng ka lethal dose ka sephetho se seholo ho 1000 ea/mL (bapisoa le sehlopha sa taolo, 33.33±1.86 vs 18.34±2.02, P<0.05). Tlhahlobo ea blot ea Bophirimela e bontša hore Tβ4 e khothalletsa phosphorylation ea Akt Ser473 le eNOS Ser1177., hape e bonts'a likamano tse itšetlehileng ka lethal dose. Akt siRNA le eNOS siRNA ka bobeli li thibela haholo litlamorao tsa pro-angiogenic tsa Tβ4 ho EPCs..
- Kalafo ea maqeba a letlalo
- Kalafo ea likotsi tsa pelo le cerebrovascular
- Kalafo ea likotsi tsa mahlo
- Lisebelisoa tse ling
Ka lebaka la mesebetsi ea eona ea tlhaho, ho kenyelletsa ho khothaletsa ho falla ha lisele tsa endothelial, ho thibela apoptosis ea lisele, litlamorao tse khahlanong le ho ruruha, le ho khothalletsa tsoelo-pele ea follicle ea moriri, Tβ4 e boetse e bonts'a monyetla o moholo oa ho hlokomela letlalo, ho loantša botsofali ba letlalo, le ho khothaletsa kholo ea moriri, har'a likarolo tse ling tsa tlhokomelo ea bophelo.
