Cux1 shghly expressed the developng kdney, wthhghest expressorestrcted towards the nephrogenc zone.As development proceeds, the amounts of Cux1 reduce wth only minimal amounts of Cux1 detected adult kdneys.Cux1 regulates the cell cycle by transcrptonally repressng the cycldependent knase nhbtors p21 and p27.hgh charges of cell prolferatoare one particular of the strkng characteristics of cyst epthelal cells polycystc kdney dsease, a lfe threatenng genetc dsease.PKD cabe nherted two dfferent kinds, aautosomal recessve type, or aautosomal domnant form, the two characterzed by flud fled cysts prmary the kdneys.ADPKD results from mutatons ether of the two genes, PKD1 or PKD2, whe mutatons a sngle locus, PKHD1, are responsble for ARPKD.Polycystn1, the proteproduct of PKD1 co localzes wth complexes nvolved cell to cell and cell to extracellular matrx nteractons.These complexes turhave a regulatory position cell prolferaton.Polycystn1 also nteracts wth Polycystn2, the proteproduct of PKD2, to nduce p21, a transcrptonal target of repressoby Cux1.
Several murne modelshave beedescrbed for PKD.A nicely characterzed murne model of PKD s the cpk mouse model.The dsease s transmtted a recessve fashoand t displays a strkng resemblance tohumaARPKD terms of cyst localzatoand dsease progresson.A targeted mutatothe Pkd1 genehas also beedescrbed.The Pkd1 null mce whch arehomozygous for ths mutatopresent wth kdney cysts and de embryoncally.Cux1 s upregulated the kdneys of each the cpk as well as the Pkd1 null mouse versions.Cells fromhumaADPKD reversible Chk inhibitor kdneys also display ncreased expressoof Cux1.Analyss of cpk along with the Pkd1 null mouse designs showed a strkng dfference betweethe expressoof Cux1, p21, p27, likewise as, cell prolferatoand apoptoss.Kdneys from Pkd1 null embryos showed ncreased expressoof Cux1.having said that, the kdneys of cpk mce, Cux1 upregulatowas not observed unt late stages of cystogeness.Whe Everolimus RAD001 p21 was not detected embryonc kdneys from Pkd1 null mce, Cux1 and p21 have been co expressed cyst lnng cells cpk mce.
contrast to the reduced expressoof p27 kdneys from Pkd1 null embryos, we noticed ancrease p27 expressothe cpk kdneys durng late stages of cystogeness.Apoptoss was also ncreased the cpk kdneys durng late stages of cystogeness.These effects suggested a model whch cystogeness proceeds as a result of dfferent mechansms the Pkd1 null mce and cpk mce.however, snce the Pkd1 null mce ded embryoncally, our analyss of cystogeness that mouse model was restrcted http://t.co/MfAIst4oCe
— Lasyaf Hossain (@lasyafhossain) November 8, 2013
for the earlest stages of cystogeness.order to analyze the role of Cux1 ADPKD beyond the embryonc phases of cystogeness, we examned a mouse model wth a collectng duct specfc deletoof the Pkd1 gene.Early stages of cystogeness ths mouse model showed ancrease Cux1 expressothat correlated wth ncreased cell prolferaton.more advanced stages of cystogeness, the ncreased expressoof Cux1 was assocated wth ancrease apoptoss.