Qhov tseem ceeb ntawm Wnt-catenin Signaling nyob rau hauv Hypertensive raum Kab Mob

Wnt/ -cateninKev taw qhia yog txoj hauv kev tau txais txiaj ntsig zoo thoob plaws hauv evolution thiab ua lub luag haujlwm tseem ceeb hauv ntau cov txheej txheem lom neeg, xws li kev loj hlob ntawm embryonic, metabolism, thiab qog nqaij hlav. Txoj cai ntawm Wnt / -catenin signaling yog qhov nyuaj. Muaj ntau yam ligands thiab receptors thiab ntau downstream effectors, nrog rau txoj kev canonical thiab noncanonical. Kev saib xyuas ntawm intracytoplasmic -catenin qib yog nyob rau hauv kev tswj nruj ntawm cov protein complex uas suav nrog glycogen synthetase kinase (GSK)-3 . Nyob rau hauv canonical Wnt signaling, Wnt khi rau lub frizzled receptor uas phosphorylates disheveled protein (Dsh / Dvl), uas nyob rau hauv lem phosphorylates thiab inactivates GSK -3 . Qhov no ua rau kev hloov pauv ntawm catenin mus rau lub nucleus, qhov uas nws ua raws li cov coactivator rau transcription yam T-cell factor thiab lymphoid enhancer factor thiab tsav cov kev qhia tshwj xeeb ntawm lub hom phiaj noob. Wnt/ -catenin signaling yog qhib rau ntau hom hlwb hauv cov qauv kab mob. Wnt / -catenin signaling pathway yog qhib rau hauv ntau cov txheej txheem pathobiological koom nrog hauv cov ntaub so ntswg fibrosis [1, 2]. Lub activation ntawmWnt/ -cateninKev taw qhia ua rau lub voj voog ntawm tes raug ntes nyob rau theem G2 / M, ua rau kev tsim cov khoom loj ntawm kev loj hlob, suav nrog cov ntaub so ntswg loj hlob - thiab cov ntaub so ntswg loj hlob [3]. Ntau qhov kev tshawb fawb tau pom tias Wnt / -catenin signaling raug tswj li cas. Nyob rau hauv lub xub ntiag ntawm lub raum kev raug mob, secretory Klotho qhia txo. Yog li ntawd, Wnt / -catenin signaling nce, thiab fibrosis tsim. Klotho protein ntau overexpression attenuates Wnt / -catenin signaling nyob rau hauv proximal tubular cells thiab peritoneal membrane [3, 4], qhov uas nws ua raws li ib tug teeb liab transduction yam uas induces noob koom nyob rau hauv cellular proliferation thiab sib txawv, thaum kawg ua rau cov ntaub so ntswg fibrosis.

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Nyob rau hauv xyoo tas los no, kev tshawb fawb txog kev siv cov qia hlwb thiab cov tshuaj suav tshuaj ntsuab rau kev kho mob ntawmkab mob raumtau txais txiaj ntsig zoo. Lub ntsiab mechanism ntawm ob txoj kev kho mob yog los txhawb kev kho mob raum cov ntaub so ntswg thiab tiv thaiv covtshuav lub raum ua haujlwm. Cov tshuaj suav tshuaj ntsuab, cistanche, tau siv hauv cov tshuaj suav tshuaj los kho ntau yammob raum mobtxij thaum ub los. Nws tau tshaj tawm tias cistanche muaj peev xwm txo tau qhov mob, txo lub raum fibrosis, thiab txhawb cov synthesis ntawm extracellular matrix Cheebtsam. Nws tau raug tshaj tawm tias cov teebmeem no yog vim nws cov khoom siv bioactive, suav nrog ntau cov tshuaj phenolic, triterpenoids, thiab coumarins.

Ntawm qhov tod tes, stem cell technology tau ua rau muaj kev hloov pauv hauv kev kho mob. Kev tshawb fawb tau pom tias cov qia hlwb tuaj yeem sib txawv rau ntau hom ntawm lub raum hlwb thiab ua cov haujlwm kho mob, suav nrog kev tiv thaiv cov ntaub so ntswg raum, ua kom cov nqaij mos fibrosis, thiab kho cov ntaub so ntswg puas.Thaum kawg, kev sib xyaw ntawm cov tshuaj suav tshuaj suav nrog kev tshawb fawb niaj hnub tuaj yeem yog tus yuam sij rau kev kho ntau yamkab mob raum.Cov tswv yim no tau maj mam lees txais los ntawm cov neeg kho mob thiab cov kev tshawb fawb tau pom tias kev kho mob ua ke ntawm cistanche thiab qia cell kho yuav txo tau qhov kev tuag ntawm cov neeg tuag.kab mob raum.

Hauv kev xaus, kev siv ntawmcistanchethiab qia cell kho hauv kev kho mob ntawmkab mob raumqhia tau hais tias muaj peev xwm zoo thiab xav tau kev tshawb fawb ntxiv. Kev sib xyaw ua ke ntawm ob txoj kev kho mob tuaj yeem muab kev kho mob zoo dua rau cov neeg uas tab tom ntsibkab mob raum.

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Kasacka et al. aim kom to taub lub luag hauj lwm ntawmWnt/ -cateninsignaling nyob rau hauv hypertensivekab mob raum. Txog rau qhov kawg no, lawv tau txiav txim siab qhov kev qhia ntawm Wnt / -catenin signaling nyob rau hauv ob peb tus qauv hypertensive nas. Cov theem pib ntawm WNT4 thiab Fzd8 tau siab dua hauv cortex dua li hauv medulla, tab sis -catenin qhia yog tib yam. Qhov no qhia tias-cateninTej zaum yuav raug tswj los ntawm cov txheej txheem sib txawv hauv lub cortex thiab medulla. Raws li ob peb lub tswv yim koom nrog hauv kev txhim kho lossis kev saib xyuas cov ntshav siab, cov qauv kub siab sib txawv muaj cov txheej txheem sib txawv ntawm kev puas tsuaj. Vim li no, cov kws sau ntawv tau tshawb xyuas ntau tus qauv kub siab.

Lub renin-angiotensin system (RAS) ua lub luag haujlwm tseem ceeb hauv kev tswj tsis tau cov ntshav siab nkaus xwb tab sis kuj ua rau kub siab. Ntshav siab tuaj yeem muab faib ua ob hom, nyob ntawm kev ua renin [5]. RAS yog tswj los yog ua rau qee lossis tag nrho cov ntshav siab hauv cov neeg mob feem ntau. SHR thiab 2K1C kab mob ntshav siab qauv nas, uas tau siv hauv Kasacka li al. txoj kev tshawb fawb, yog cov qauv kev ua haujlwm siab renin siab. Hauv cov qauv nas no, Wnt4 thiab -catenin qhia hauv tubules tau ntau dua li cov nas hauv DOCA-ntsev, uas yog cov qauv kub siab nrog kev ua haujlwm qis renin. GSK-3 kev qhia coj txawv txawv hauv SHRs thiab DOCA-ntsev nas thiab tau nce hauv tubules tsuas yog tom kawg. Qhov no qhia tias RAS tuaj yeem cuam tshuam rau kev ua haujlwm ntawm Wnt / -catenin signaling.

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RAS-catenin cuam tshuam tsis ntev los no tau tshaj tawm. Wnt / -catenin signaling thiab RAS kev ua haujlwm tau pom tias muaj kev tswj hwm hauv lub raum laus [6], uas Klotho downregulation tuaj yeem cuam tshuam rau catenin signaling. Tsis tas li ntawd,Wnt/ -cateninyog ib tug ntawm cov regulators uas tswj ntau RAS noob. Ntawm qhov tod tes, Kasacka et al. pom tias qhov kev qhia ntawm cov proteins uas muaj feem xyuam nrog catenin tau nce hauv RAS ua qauv, xws li 2K1C thiab SHR. Qhov no qhia tau hais tias RAS tswj cov catenin ntsig txog protein qhia. Tom ntej no, cov kws sau ntawv tau txiav txim siab txog cov txheej txheem ntawm cov kev sib cuam tshuam ntawm cov hom ntshav siab thiab Wnt / -catenin signaling activation. Lawv kuj tau tham txog lub luag haujlwm ntawm oxidative kev nyuaj siab vim tias ntau qhov kev tshawb fawb tau pom tias nws muaj feem cuam tshuam rau txoj kev loj hlob ntawmraum puas[7]. Ntxiv mus, oxidative kev nyuaj siab cuam tshuam rau Wnt / -catenin signaling. Kev khi ntawm Dvl rau thioredoxin zoo li protein nucleoredoxin (NRX) nyob ntawm NRX kev ua, vim tias kev hloov pauv ntawm ob lub catalytic cysteine cuam tshuam Dvl khi. Tsis tas li ntawd, kev khi yog inhibited los ntawm kev kho mob nrog hydrogen peroxide, uas qhia tias Dvl-NRX kev sib cuam tshuam yog tswj los ntawm oxidative kev nyuaj siab. Interestingly, NRX yog ib tug muaj zog inhibitor ntawm Wnt / -catenin signaling [8].

Kev tshawb fawb tsis ntev los no tau qhia qhov tseem ceeb ntawmWnt/ -cateninteeb liab hauvkab mob raumkev loj hlob, tshwj xeeb tshaj yog kev hloov pauv ntawm fibrotic (Fig. 1). Tsis tas li ntawd, nws tau raug tshaj tawm tias cannabinoid receptor hom 2 thiab -catenin koom tes los txhawb lub raum fibrosis [9]. Wnt / -catenin signaling kuj tau pom los ua lub luag haujlwm tseem ceeb hauv kev txhim kho glomerular sclerosis thiab tubulointerstitial lesions. Yog li, kev tshawb fawb txog lub luag haujlwm ntawm Wnt / -catenin signaling nyob rau hauv cov kab mob hauv lub raum tsis tu ncua thiab suav tias yog qhov tseem ceeb heev. Kev nkag siab txog Wnt/ -catenin signaling yog ib qho tseem ceeb rau kev txiav txim siab cov hom phiaj kho mob, thiab kev tshawb fawb ntxiv yuav tsum tau ua raws li qhov kev tshawb pom ntawm Kasacka li al. Tsis tas li ntawd, kev sib raug zoo ntawm RAS thiab Wnt / -catenin signaling yog qhov tseem ceeb rau kev nkag siab txog kev ua tau zoo ntawm cov kev kho mob uas twb muaj lawm. Yog li ntawd, nws yog ib qho tseem ceeb kom nthuav tawm lub hauv paus txheej txheem ntawm -catenin activation los ntawm RAS.

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Ua raws li cov qauv kev coj ncaj ncees

Kev tsis sib haum xeebTus sau tshaj tawm tsis muaj kev sib tw nyiam.

Publisher daim ntawvSpringer Nature tseem nyob nruab nrab hais txog kev txiav txim plaub ntug hauv daim duab qhia kev tshaj tawm thiab cov koom haum koom nrog.

Cov ntaub ntawv

1. Surendran K, Schiavi S, Hruska KA. Wnt-dependent beta-catenin signaling yog qhib tom qab unilateral ureteral obstruction, thiab recombinant secreted frizzled-related protein 4 hloov qhov kev loj hlob ntawm lub raum fibrosis. J Am Soc Nephrol. 2005; 16:2373–84.

2. Kadoya H, Satoh M, Nagasu H, Sasaki T, Kashihara N. Deficiency ntawm endothelial nitric oxide signaling pathway exacerbates peritoneal fibrosis nyob rau hauv nas. Clin Exp Nephrol. 2015; 19:567–75.

3. Satoh M, Nagasu H, Morita Y, Yamaguchi TP, Kanwar YS, Kashihara N. Klotho tiv thaiv nas lub raum fibrosis los ntawm inhibiting Wnt signaling. Am J Physiol Ren Physiol. Xyoo 2012; 303:F1641–51.

4. Kadoya H, Satoh M, Nishi Y, Kondo M, Wada Y, Sogawa Y, et al. Klotho yog lub hom phiaj kho tshiab hauv peritoneal fibrosis ntawm Wnt signaling inhibition. Nephrol Dial Transpl. 2020; 35:773–81.

5. Laragh JH, Letcher RL, Pickering TG. Renin profileing rau kev kuaj mob thiab kev kho mob ntshav siab. JAMA. 1979; 241:151–6.

6. Miao J, Liu J, Niu J, Zhang Y, Shen W, Luo C, et al. Wnt/beta-catenin/RAS signaling mediates lub hnub nyoog ntsig txog lub raum fibrosis thiab cuam tshuam nrog mitochondrial dysfunction. Kev laus Cell. Xyoo 2019; 18: e13004.

7. Nagasu H, Satoh M, Kiyokage E, Kidokoro K, Toida K, Channon KM, et al. Ua kom cov endothelial NAD(P)H oxidase accelerates glomerular raug mob nyob rau hauv cov nas mob ntshav qab zib. Lab Invest.2016;96:25–36.

8. Funato Y, Michiue T, Asashima M, Miki H. Cov thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-beta-catenin signaling los ntawm disheveled. Nat Cell Biol. 2006; 8:501–8.

9. Zhou S, Wu Q, Lin X, Ling X, Miao J, Liu X, et al. Cannabinoid receptor hom 2 txhawb rau lub raum fibrosis los ntawm orchestrating beta-catenin signaling. Raum Int. 2021; 99:364–81.

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