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FunkcijaUredi

LIF citokin je dobio ime po njegovoj sposobnosti da indukuje terminalnu diferencijaciju ćelija mijeloidne leukemije. Druge osobine ovog citokina su: promocija rasta i ćelijske diferencijacije različitih tipova ciljnih ćelija, uticaj na koštani metabolizam, kaheksiju, neuronski razvoj, embriogenezu i inflamacija. Za p53 regulisani LIF je bilo pokazano da omogućava implantaciju u mišjem modelu.[1][2]

Vezivanje/aktivacijaUredi

LIF se vezuje za specifični LIF receptor (LIFR-α) koji formira heterodimer sa specifičnom podjedinicom zajedničkom za sve članove te familije receptora, GP130 podjedinicom signalne transdukcije. Ovo dovodi do aktivacije JAK/STAT (Janus kinaza/signal transducer i aktivator transkripcije) i MAPK (mitogenom aktivirana proteinska kinaza) kaskade.

EkspresijaUredi

LIF je normalno izražen u trofektodermu embriona u razvoju. Njegov receptor LIFR je izražen širom unutrašnje ćelijske mase. Pošto su embrionske stem ćelije izvedene iz unutrašnje ćelijske mase u stupnju blastocista, njihovo uklanjanje iz unutrašnje ćelijske mase takođe uklanja njihov LIF izvor.

Upotreba u stem ćelijskim kulturamaUredi

LIF odstranjivanje potiskuje stem ćelije ka diferencijaciji, ali one zadržavaju svoj proliferativni potencijal ili pluripotentnost. Iz tog razloga LIF se koristi u mišjim embrionskim stem ćelijskim kulturama. On je neophodan za održavanje stem ćelija u nediferenciranom stanju. Moguće je genetskim manipulacijom embrionskih stem ćelija omogućiti LIF nezavisni razvoj, posebno prekomernim izražavanjem gena Nanog.

LIF nije neophodan za kulture ljudskih embrionskih stem ćelija.[3] [4]

ReferenceUredi

  1. Wenwei Hu, Zhaohui Feng, Angelika K. Teresky1, Arnold J. Levine (November 29, 2007). "p53 regulates maternal reproduction through LIF". Nature 450: 721–724. 
  2. Mire-Sluis, Anthony R.; Thorpe, Robin, ur. (1998). Cytokines (Handbook of Immunopharmacology). Boston: Academic Press. ISBN 0-12-498340-5. http://www.sciencedirect.com/science/book/9780124983403. 
  3. Kawahara Y, Manabe T, Matsumoto M, Kajiume T, Matsumoto M, Yuge L (2009). "LIF-free embryonic stem cell culture in simulated microgravity". PLoS ONE 4 (7): e6343. PMC 2710515. PMID 19626124. doi:10.1371/journal.pone.0006343. 
  4. "CGS : PTO Finds Stem Cell Patent Anticipated, Obvious in Light of 'Significant Guideposts'". http://www.geneticsandsociety.org/article.php?id=5197. 

LiteraturaUredi

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Spoljašnje vezeUredi