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Kev Tswj Xyuas Thaum Ntxov Lub Raum Pob Zeb: TGF- 1 Kev Qhia

Mar 19, 2022

Yog xav paub ntxiv:ali.ma@wecistanche.om



Ntu Ⅱ: Phosphatidylserine eversion tswj los ntawm phospholipid scramblase qhib los ntawm TGF- 1/Smad signaling nyob rau theem pib ntawm lub raum pob zeb tsim

Xiu Guo Gan1 · Hai Tao Xu1 · Zhi Hao Wang

Abstract

Cov txheej txheem hauv qab phosphatidylserine eversion nyob rau hauv lub raum tubule hlwb tom qab calcium oxalate-mediated kev puas tsuaj tseem tsis meej; yog li ntawd, peb tau tshawb xyuas cov teebmeem ntawmTGF- 1/Smad signaling ntawm phosphatidylserine eversion nyob rau hauv lub raum tubule cell membrane thaum ntxov ntawmlub raum pob zebkev loj hlob. Nyob rau hauv cov qauv nas ntawm cov theem pib ntawm calcium oxalate pob zeb tsim, phosphatidylserine eversion ntawm lub raum tubular cell membrane tau kuaj pom los ntawm kev ntws cytometry, thiab kev qhia ntawmTGF- 1(transforming growth factor- 1), Smad7, thiab phospholipid scramblase nyob rau hauv lub raum tubular cell membrane yog ntsuas los ntawm western blotting. Peb pom tias covTGF- 1/ Smad signaling pathway nce phosphatidylserine eversion ntawm cov kab mob. Cov txiaj ntsig ntawm kev tshawb fawb hauv vitro tau pom tias oxalate raug rau lub raum tubule hlwb ntxias TGF-1 qhia, nce phospholipid scramblase kev ua haujlwm thiab phosphatidylserine eversion hauv lub raum tubule cell membrane. Cov txiaj ntsig no qhia tiasTGF- 1stimulates phosphatidylserine eversion los ntawm kev nce phospholipid scramblase kev ua haujlwm hauv lub raum tubule cell membrane thaum lub sijhawm ntxov ntawmlub raum pob zebkev loj hlob. Cov txiaj ntsig ntawm txoj kev tshawb fawb no tsim lub hauv paus rau kev tshawb fawb ntxiv txog kev txhim kho cov tshuaj kho mob tshwj xeeb uas kho urolithiasis thiab ua rau muaj kev cuam tshuam tsawg dua.

Ntsiab lus:Phospholipid scramblase. Phosphatidylserine.Lub raum pob zeb.TGF- 1


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NYEM QHOV NO RAU PART Ⅰ

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Kev sib tham

Txog niaj hnub no, kev tshawb fawb tsiaj tsis tau tsom mus rau lub luag haujlwm ntawm PS hauvlub raum pob zebtsim los yog hais txog seb qhov kev tshawb pom ntawm cov kev tshawb fawb hauv vitro txhais rau cov tsiaj hauv cov tsiaj. Yuav kom tau txais txiaj ntsig zoo dua, kev tshawb fawb siv hauv vitro qauv yog qhov zoo dua. Hauv peb cov qauv nas ntawm cov pob zeb CaOx thaum ntxov, lubTGF- 1qib thiab PS-eversion tus nqi nyob rau hauvlub raum pob zebpawg tau nce, uas yog raws li cov txiaj ntsig tau txais ntawm qib cellular, qhia tias nrog nce oxalic acid concentration, concomitant nce nyob rau hauv cell membrane-PS eversion tso cai rau crystals mus rau lub cell membrane [28]. Yog li, peb tau lees paub tias cov kev tshawb fawb cytological saum toj no tsim nyog rau kev tshuaj xyuas tus qauv nas. Peb pom tias oxalate nws tus kheej raug mob rau cov hlwb thiab tias nws tuaj yeem ua tus neeg sawv cev tseem ceeb rau kev txhawb nqa.TGF- 1. Tsis tas li ntawd, lubTGF- 1qib thiab PS externalization tau cuam tshuam los ntawm SB431542, tawm tswv yim tiasTGF- 1/Smad signaling pathway pab txhawb PS Externalization ntawm lub cev-ism theem. Progressive activation ntawm NAD(P)H oxidase nyob rau hauv lub raum tubular hlwb ntawm induction ntawmTGF- 1, yog lub peev xwm molecular mechanism ntawmTGF- 1/Smad signaling-induced ROS ntau lawm [7], whereas ROS mediated tsub zuj zuj ntawm MRP-1 los yog BCRP plays lub luag hauj lwm tseem ceeb hauv oxalate-induced PS externalization nyob rau hauv lub raum epithelial cell membrane [23]. Yog li ntawd, peb xaus lus tias lub mechanism ntawmTGF- 1/Smad signaling-induced PS eversion nyob rau hauv lub raum tubular epithelial hlwb yog kho los ntawm oxidative kev nyuaj siab los ntawm ROS.

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Thaum LLC-PK1 hlwb raug kho nrog 1 mmol potassium oxalate (Kox) rau 6,12,24, lossis 48 h, Khan li al.dev tsis pom qhov hloov pauv loj ntawm apoptotic morphological hauv cov hlwb tom qab 6h ntawm kev kho oxalate. Txawm li cas los xij, tom qab 12h ntawm qhov raug, lawv tau pom cov kev hloov pauv tseem ceeb xws li condensation thiab margination ntawm nuclear chromatin, DNA fragmentation, thiab PS kev tsiv teb tsaws hauv cov plasma membrane bilayer los ntawm sab hauv mus rau ntawm tes [8]. Hauv peb txoj kev tshawb fawb dhau los, peb tau pom tias { {10}}.5 mmol oxalates ua rau lub sij hawm-thiab concentration-nyob ntawm qhov nce hauv PS externalization nyob rau hauv MDCK raum epithelial cell kab [2].Nyob rau hauv txoj kev tshawb no, 0.5 feem pua ​​​​CaOx tau siv rau lub hlwb, thiab PS-eversion tus nqi nce nyob rau hauvlub raum pob zebpab pawg. Txawm hais tias cov cell membrane PS tau hloov pauv hauv peb txoj kev tshawb fawb tam sim no, cov hlwb no yuav tsum tsis txhob muaj apoptosis. PS eversion yog ib qho tseem ceeb ntawm qhov cim ntawm apoptosis. Cov kev tshawb fawb tsis ntev los no tau pom tias apoptosis thiab PS eversion yog ob qhov xwm txheej ywj pheej, uas yog, apoptotic hlwb tsis tas yuav qhia PS eversion thiab PS-eversion hlwb tsis tas yuav apoptotic [29]. Nws tsis tsim nyog tsuas yog cia siab rau PS eversion los txiav txim seb lub cell puas yog apoptotic, vim tias cov kev tshawb fawb tau tshaj tawm PS raug rau hauv cov hlwb uas tsis yog apoptotic [30-32].

Nyob rau hauv txoj kev tshawb no, ib qho kev tsis txaus siab ntawm PLSCR tau kuaj pom nyob rau hauv pawg tswj cov hlwb, thaum cov protein no tau nce ntau hauv pawg CaOx, qhia tias muaj ntau dhau ntawm PLSCR. Cov txiaj ntsig no tau ua raws li qhov kev tshawb pom ntawm Singireesu thiab al.hais txog cov txiaj ntsig muaj txiaj ntsig zoo ntawm DHCL ntawm lub raum hlwb[33]. Thaum cov hlwb hauv CaOxgroup tau kho nrog cov tshuaj tiv thaiv.TGF- 1cov tshuaj tiv thaiv kab mob, qib ntawm PLSCR tau txo qis, qhia tias kev ua kom PLSCR tau kho los ntawmTGF- 1. Tsis tas li ntawd, peb tau soj ntsuam kev txhawb zog sab nraud ntawm NBD-PS hauvTGF- 1pab pawg thiab CaOx pawg. Thaum lub raum tubular epithelial hlwb los ntawm cov pab pawg no tau kis nrog PLSCR siRNA, tus PS internalization tus nqi nce, whereas externalization tus nqi txo, qhia tias.TGF- 1ua rau PSexter-finalization nyob rau hauv lub raum tubule cell membrane los ntawm activating PLSCR nyob rau hauv lub raum tubule cell membrane hauv vitro. Ua ke, oxalate raug rau lub raum tubule hlwb inducesTGF- 1qhia, ua rau muaj ROS ntau lawm ntawm NAD(P)H oxidase; ROS ces hloov cov haujlwm ntawm PLSCR [9,10]. Thaum kawg, PLSCR ua rau PS externalization nyob rau hauv lub raum tubule cell membrane, raws li pom nyob rau hauv peb txoj kev tshawb no.

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Ib txoj kev tshawb fawb yav dhau los tau qhia tias kev kho oxalate tsis qhib PLSCR hauv MDCK cov hlwb hauv vitro, vim PLSCR kev ua kom muaj zog cytoplasmic Ca2, thiab oxalate rap-idly txo qis intracellular Ca2 ntxiv rau cov concentration hauv MDCK hlwb [2]. Qhov kev xav no tau txhawb nqa los ntawm cov txiaj ntsig ntawm kev tshawb fawb tam sim no. Qhov ntawd yog, txawm hais tias txoj kev tshawb fawb yav dhau los tau qhia txog qhov cuam tshuam ntawm oxalic acid, ntau dua li CaOx, ntawm lub raum tubular epithelial hlwb, peb pom tias Ca2 ntxiv rau cov concentration nce hauv lub raum khaws cov kab ke thaum ntxov ntawm CaOx pob zeb kev loj hlob hauv tus qauv nas. Raws li PLSCR raug nthuav tawm dhau ntawm cov cell membrane, peb ntseeg tias PLSCR tuaj yeem ua haujlwm los ntawm Ca2 hauv lub raum khaws cov kab ke es tsis yog los ntawm intracellular Ca2 ntxiv.

Nyob rau hauv physiological tej yam kev mob, asymmetric faib ntawm phospholipids nyob rau hauv lub eukaryotic cell membrane, uas yuav tsum tau aminophospholipid translocase (APLT) thiab PLSCR los ua ib tug synergistic lub luag hauj lwm, yog tsim nyog rau lub cell membrane ua nws physiological functions [34] .Hauv qhov kev sim no, peb xav txog. qhov piv ntawm PS eversion nyob rau hauv lub cell membrane los qhia cov kev ua ntawm PLSCR. Vim tias APLT tau raug lees paub tias yog ib qho ntawm cov xwm txheej ua rau PS eversion, APLT cuam tshuam qhov kev ntsuas ntawm PLSCR enzyme kev ua hauv qhov kev sim no. Cov kev tshawb fawb soj ntsuam ntxiv yuav tsum tau lees paub tias yuav ua li cas APLT thiab PLSCR ua haujlwm ua ke hauv PS eversion ntawm lub raum tubular cell mem-brane, thiab txheeb xyuas lwm yam uas tswj PS eversion kom nkag siab zoo dua cov txheej txheem hauv qab.lub raum pob zebtsim.


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Cov lus xaus

Kev raug CaOx tuaj yeem ua rau muaj kev txhim kho ntawmTGF- 1, uas tom qab activates ROS nyob rau hauv lub raum tubular hlwb; ROS ces ua kom muaj zog PLSCR, sawv cev rau ib qho ntawm cov txheej txheem loj uasTGF- 1-ROS signaling stimulates PS externalization nyob rau hauv lub raum tubule cell membrane thaum ntxov ntawmlub raum pob zebkev loj hlob. Cov txiaj ntsig ntawm txoj kev tshawb fawb no tsim lub hauv paus rau kev tshawb fawb ntxiv txog kev txhim kho cov tshuaj kho mob tshwj xeeb uas kho urolithiasis thiab ua rau muaj kev cuam tshuam tsawg dua.


Cov ntaub ntawv

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