Ths suggests that reduction of endogenous B catenncreases mortalt

Ths suggests that reduction of endogenous B catenncreases mortalty price mce just after AK.the survvng mce, serum creatnne ranges at 2 days immediately after folc acd have been sgnfcantlyhgher KsB cat mce thathat the controls.Accordngly, KsB cat kdneys exhbted far more significant morphologcal njury, partcularly the outer strpe of out medulla regon, characterzed by reduction of brush border, tubular Smad2 inhibitor cell depletoand cast formatothe lumen.Quanttatve evaluation of kdney morphologcal njury betweecontrol and KsB cat groups at two days just after folc acd njectos presented Fgure 4c.With each other, clear that reduction of endogenous B catenaggravates tubular lesons and acute kdney faure nduced by folc acd.Ablatoof B catenpromotes tubular cell apoptoss and Bax expressoTo investigate the mechansm underlyng the cytoprotectve role of endogenous B catenAK, we even more examned apoptotc cell death the kdneys of control and KsB cat mce following folc acd njecton.As showFgure 5a, TUNEL stanng uncovered consderable apoptoss both cortcal and medullar regons with the kdneys manage mce at 2 days just after folc acd admnstraton.
however, the frequency of apoptoss the KsB cat kdneys was sgnfcantlyhgher thathat the controls this content beneath very same condtons.Quanttatve data oapoptotc cells the two cortcal and medullar regons of management and KsB cat mce are presented Fgure 5b.These outcomes recommend that tubule specfc loss of B catenexacerbates kdney njury by promotng apoptoss.We additional examned renal expressoand dstrbutoof Bax, a pro apoptotc member of Bcl 2 famy, manage and KsB cat mce, snce a central player medatng mtochondral dysfunctoand cell apoptoss.24, 25 As showFgure five, c and d, Bax protewas markedly ncreased the kdneys of KsB cat mce at 2 days following folc acd njecton, whecompared towards the controls.mmunohstochemcal stanng also uncovered a substantal ncrease of Bax proterenal tubules the kdneys of KsB cat mce.Ablatoof endogenous B catenactvates multple pro apoptotc pathways To elucdate the upstream sgnalng tharesponsble for Bax nductoKsB cat mce, we further examned renal expressoof p53, a tumor suppressor protethat promotes apoptoss by regulatng Bax expresson.
26 As showFgure

6, a and b, p53 protewas sgnfcantly upregulated the kdneys of KsB cat mce at two days after folc acd njecton, comparng wth the controls.These data suggest that p53 upregulatocould be a potental upstream sgnalng that leads to renal Bax nductoKsB cat mce after njury.Bax protes also subjected to regulatoby Akt medated phosphorylaton.27 Therefore, we also examned the phosphorylatostatus of renal Akt vvo.As showFgure 6c, tubule specfc reduction of B catensubstantally nhbted Akt phosphorylatoat Serne 473 the KsB cat mce, although total Akt abundance was unaltered.

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