adamianis Tirkmlis avTvisebiani simsivnuri ujredebis genebis eqspresiaze TeTri virTagvas Tirkmlis Termostabiluri cilovani faqtoris zemoqmedebis Seswavla

 

a.      mefariSvili, p.xuroZe, m.CxobaZe, d.ZiZiguri, T.CigogiZe, l.managaZe

 

iv. javaxiSvilis saxelobis Tbilisis saxelmwifo universiteti, 

urologiis erovnuli centri

 

    

Sesavali. dReisaTvis aqtiurad Seiswavleba iseTi ujredebis gamravlebis makontrolebeli meqanizmebi, romelTa TviTganaxlebis unari zrdasrul mdgomareobaSi umniSvnelo donezea SenarCunebuli. am mxriv gansakuTrebiT sainteresoa Tirkmlis epiTeliocitebi. literaturuli monacemebis Tanaxmad, wyvili organodan erT-erTis amokveTis an dazianebis SemTxvevaSi sawyis etapze Tirkmlis adaptaciuri zrdis erT-erTi ZiriTadi forma aris ujreduli hipertrofia. ujredebis gamravleba SedarebiT gvian vadebze, operaciidan 48-e da 72-e saaTebze  aRiniSneba (1, 2), rac imaze miuTiTebs, rom zrdasruli Tirkmlis epiTeliocitebi inarCuneben gamravlebis unars. dReisaTvis ZiriTadad aRwerilia maTi gamravlebis mastimulirebeli faqtorebi (6, 11). zemoT Tqmulidan gamomdinare, Cveni samuSaos mizani iyo TeTri virTagvas Tirkmlis epiTeliocitebis zrdis Semakavebeli endogenuri faqtoris identificireba da misi moqmedebis meqanizmis dadgena.

 masala da meTodebi. eqsperimentebSi gamoyenebuli iyo zrdasruli (120-140g) da eqvsdRiani (10g) TeTri araxazovani virTagvebi. Tirkmlis qsovilidan birTvebis izolirebas vaxdendiT georgievisa da sxvaTa mier modificirebuli Sovos meTodiT (3). birTvebSi dnm-s raodenobas vsazRvravdiT sadovskisa da sternis (7) mixedviT. izolirebuli birTvebis sistemaSi rnm-s sinTezis intensiurobaze vmsjelobdiT mJavaSi uxsnad fraqciaSi 14C-utf-s CarTvis intensiurobis cvlilebis mixedviT. zrdasruli virTagvas Tirkmlis qsovilidan cilebis miRebas da Termul damuSavebas vawarmoebdiT adre aRwerili meTodis Tanaxmad (8). eqsperimentebSi gamoyenebuli iyo agreTve al.wulukiZis sax. urologiis erovnuli centridan miRebuli adamianis postoperaciuli masala.

miRebuli Sedegebi da maTi ganxilva. zrdasruli virTagvas Tirkmlis qsovilidan spirtuli eqstraqciis meTodiT miRebuli  Termostabiluri  cilovani fraqciis (81°-ani fraqcia) moqmedebis meqanizmis dadgenis mizniT, Tavdapirvelad SeviswavleT misi zemoqmedeba Tirkmlis epiTeliocitebis mitozur aqtiurobaze. arsebuli monacemebis mixedviT, terminalurad diferencirebuli Tirkmlis ujredebis zrdis makontrolebeli meqanizmebis Sesaswavlad farTod gamoiyeneba proliferirebadi epiTeliocitebi nefrogenezis sxvadasxva etapze (4, 9). aqedan gamomdinare, liofilizirebuli 81°-iani cilovani fraqcia (200g) intraperitonialurad SeviyvaneT eqvsdRian virTagvebSi. gamovlinda, rom endogenuri cilovani fraqciis zemoqmedebis Sedegad proliferirebadi Tirkmlis epiTeliocitebis mitozuri indeqsi 25%-iT mcirdeba sakontrolo maCvenebelTan SedarebiT (suraTi 1). miRebuli Sedegebidan gamomdinareobs, rom zrdasruli TeTri virTagvas Tirkmlis qsovili Seicavs epiTeliocitebis gamravlebis mainhibirebel cilovani bunebis faqtors.

cnobilia, rom zrdis faqtorebi ujredis zedapirze specifikur receptorebTan urTierTqmedebis gziT ujredis SigniT signalis   gadacemas uzrunvelyofen. zrdis faqtorebiT ganxorcielebuli signalis transduqcia birTvSi transkripciis faqtorebis sinTezs uzrunvelyofs, romlebic Tavis mxriv gamravlebis makontrolebeli genebis produqtebis eqspresias iwveven (5). ukanaskneli wlebis monacemebiT, zogierTi receptori (magaliTad, angiotenzinis AT2-receptori) signalis transduqciaSi monawile proteinkinazebis aqtiurobis inhibirebis gziT proqsimaluri milakis epiTeliocitebis proliferaciis daTrgunvas ganapirobeben (10).

      aRniSnulidan gamomdinare, vivaraudeT rom Cvens mier zrdasruli Tirkmlis ujredebidan miRebuli cilovani bunebis faqtoris moqmedebac swored genebis pirveladi aqtiurobis regulaciis doneze xorcieldeba.  am mizniT,  SeviswavleT eqvsdRiani TeTri virTagvebis Tirkmlis epiTeliocitebis transkripciul aqtiurobaze aRniSnuli cilovani fraqciis zegavlena in vivo. cxovelebs intraperitonialurad SevuyvaneT aRniSnuli fraqcia, sami saaTis Semdeg movaxdineT maTi dekapitacia da Tirkmlis ujredebidan birTvebis izolireba. gamovlinda, rom cilovani fraqcia Seicavs aqtiur sawyiss, romlis moqmedeba genebsis eqspresiis doneze xorcieldeba. kerZod, rnm-sinTezis intensiuroba am fraqciiT ineqcirebuli cxovelebis ujredebSi 40%-iT qveiTdeba kontrolTan SedarebiT (suraTi 2).

      miRebuli Sedegebidan gamomdinareobs, rom zrdasruli virTagvas Tirkmlis ujredebi Seicaven Termostabilur cilebs, romelTa zemoqmedeba genebis pirveladi aqtiurobis regulaciis doneze xorcieldeba.

analogiuri Sedegebi miRebuli iyo adamianis simsivnuri Tirkmlis ujredebze. postoperaciuli masala: paTologiuri qsovili da simsivnuri keridan daSorebuli ubani, miRebuli iyo Tbilisi al. wulukiZis sax. urologiis erovnuli centridan. dadginda adamianis Tirkmlis simsivnuri qsovilidan (Tirkmelujredovani kibos naTelujredovani varianti) izolirebul birTvebSi genebis eqspresiaze virTagvas Tirkmlis cilovani faqtoris damTrgunveli zemoqmedeba. in vitro rnm-sinTezis intensiuroba aRniSnuli faqtoris zemoqmedebiT 60%-iT qveiTdeba kontrolTan SedarebiT (suraTi 3).

aRsaniSnavia, rom simsivnuri keridan daSorebuli ubnidan mopovebuli qsovilis ujredebis birTvebze faqtoris moqmedeba ar vlindeba (suraTi 4).

miRebuli Sedegebidan gamomdinare SeiZleba vivaraudoT, rom zrdasruli virTagvas Tirkmlis ujredebis cilovani faqtori xasiaTdeba saxeobrivi specifikurobiT an simsivnuri keridan daSorebuli qsovilis ujredebSi Seicvala samizne genebis miRwevadoba.

 

 

 

literatura

 

1.      hauveau J., Moule Y., Rouiller Ch. Jsolation of pure and unaltered liver nuclei: Morphology and biochemical composition,  Exp. Cell Res., 1956, V. 11, pp 317-321.

2.      Igarashi P. MD. Transcription factors and apoptosis in kidney development., Current Opinion in Neprology and Hipertenzion, 1994, v. 3, No. 3, pp. 308-317.

3.      Lodish H., Berk A., Zipursky S.L., Matsudaira P., Baltimore D., Darnell J. Molecular Cell Biology, 1999. p.1084.

4.      Paul LC, Saito K, Davidoff A, Benediktsson H. Growth factor transcripts in rat renal transplants, J. Kidney Dis., 1996, v28, pp. 441-446.

5.      Sadovsky P., Stern J. Cell  Biol., 1968, V. 37p. 147-164.

6.      Tumanishvili G., Giorgobiani N., Dzhaparidze M., Salakaia T. Proceedings of the Georgian Academy of Sciences, Biological Series, 1994, v.20, No. 1-6, pp 88-90.

7.      Woolf  S., Cale C. Roles of growth factors in renal development, Current Opinion in Neprology and Hipertenzion, 1997, v. 6, No. 1, pp. 10-14.

8.      Zimpelmann J., Burns K. Angiotsnsen II AT2 receptors inhibit growth responses in proximal tubul cells,  2001, v.281, Issue 2, pp 300-308.

9.      Walton G, Buttyan R, Garcia-montes E, Olsson CA, Hensle TW, Sawczuk IS. Renal growth factor expression during the early phase of experimental hydronephrosis, J. Urol., 1992, v148, No 8, pp. 510-514.

 

 

Summary

 

It has been established that kidney cells of a mature white rat include inhibiting albuminous factor for epiteliocytes` reproduction. It's shown that the effect of the mentioned factor is performed at the level of genes` original activity regulation. Rat`s kidney albuminous factor reveals an inhibiting effect on the nuclear transcript activity isolated from the human cells of Renal cell carcinoma (light cellular variant) as well. The factor`s inhibiting effect has not been revealed at the area far from a tumor center that may be conditioned by the limitation of target genes` exscess to mentioned cells.