Echinacoside Txhawb Kev Loj Hlob Ntawm Tib Neeg Lub raum Tubular Epithelial Cells Los Ntawm Thaiv HBX / TREM2-mediated NF-κB Txoj Kev Qhia
Mar 06, 2022
Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com
YuFan ZHanG, QinFanG Wu, liMin ZHonG, donGWei GonG
Abstract.
Tus kab mob siab B tus kab mob X (HBX) yuav tsum muaj rau kev rov ua dua ntawm HBV thiab ua lub luag haujlwm hauv kev loj hlob ntawm kab mob siab rau tib neeg. Txawm li cas los xij, lub hauv paus muaj nuj nqi ntawm HBX thaum lub sij hawm HBV-induced chronic glomerulonephritis (HBV-Gn) tsis paub. (echinacoside los ntawm cistanche)(ecH) yog phenylethanoid glycoside los ntawm Cistanche genus, uas muaj zog antiapoptosis thiab neuroprotective kev ua ub no. nyob rau hauv txoj kev tshawb no, kev ua haujlwm ntawm HBX thiab kev sib raug zoo ntawm HBX thiab ecH hauv tib neeg lub raum tubular epithelial hlwb (rTecs; HK-2 kab ntawm tes) tau tshawb nrhiav. thim rov qab-quantitative Pcr thiab western blot tsom xam tau siv los ntsuas qhov mRNA thiab protein qhia theem ntawm HBX hauv HK-2 hlwb, raws li. Cov khoom siv suav ntawm tes-8 kev soj ntsuam tau ua los tshuaj xyuas cov cell proliferation. Flow cytometry tsom xam tau siv los txiav txim tus nqi ntawm apoptosis. HBX tau pom tias muaj kev tiv thaiv proliferative thiab proapoptotic cuam tshuam hauv HK-2 cov hlwb thiab tau cuam tshuam zoo nrog kev cuam tshuam receptor qhia ntawm myeloid cell 2 (TreM2) qhia. Tsis tas li ntawd, ECH cuam tshuam txoj haujlwm ntawm HBX hauv HK-2 hlwb, ua haujlwm raws li HBX suppressor. Ntxiv mus, ib qho tshwj xeeb NF-κB inhibitor, PdTc, tau siv los tshuaj xyuas kev sib raug zoo ntawm HBX thiab nF-κB. Cov txiaj ntsig tau qhia tias nF-κB tau koom nrog hauv HBX / TreM2 kev taw qhia txoj hauv kev thiab tswj tsis zoo TreM2 qhia hauv RTECS. Txoj kev tshawb fawb tam sim no tau muab cov kev nkag siab tshiab rau kev ua haujlwm ntawm HBX, thiab tseem qhia txog qhov muaj peev xwm ntawm ECH ua tus neeg sawv cev kho mob rau HBV-Gn.
Taw qhia
Tus kab mob siab B (HBV) yog tus kab mob Hepadnaviridae, uas ua rau mob siab thiab mob ntev rau tib neeg (1). HBV, tsis tsuas yog ua rau muaj kab mob tsis tu ncua lossis ib ntus hauv daim siab tab sis kuj kis mus rau cov ntaub so ntswg extrahepatic, nrog rau cov txiav, cov kua tsib, cov kab mob lymphoid thiab ob lub raum (2). Ntxiv mus, tus kab mob HBV zoo sib xws nrog mob glomerulonephritis (HBV-Gn); Txawm li cas los xij, cov txheej txheem molecular ntawm HBV thaum HBV-Gn tsis to taub tag nrho (3,4).
HBV regulatory kab mob siab B tus kab mob X (HBX) protein yuav tsum tau rau HBV replication (5,6). ntau qhov kev tshawb fawb tau tshaj tawm tias HBX txhawb kev loj hlob ntawm tes thaum lub sij hawm HBV kis kab mob siab hepatocarcinoma (7-9). Tib neeg lub raum tubular epithelial hlwb (rTecs) yog ib feem tseem ceeb ntawm lub raum tubular interstitium thiab ua lub luag haujlwm tseem ceeb hauv lub raum mob (10). rTec apoptosis zoo sib xws nrog kev ua haujlwm tsis zoo ntawm tubular interstitium, uas tom qab ntawd ua rau kev loj hlob ntawm HBV-Gn (10). HBX feem ntau qhia nyob rau hauv rTec hlwb thiab ua rau rTec apoptosis thiab lub raum kab mob nyob rau hauv cov neeg mob uas muaj HBV-Gn (11,12). Tsis tas li ntawd, HBX tau raug tshaj tawm los txwv kev loj hlob ntawm nas rTecs (13), thiab HBX overexpression accelerates lub voj voog ntawm tes los ntawm G1 mus rau S theem hauv thawj rTecs, ua rau lub voj voog ntawm tes raug ntes nyob rau theem S (14). Yog li, kev txheeb xyuas tus HBX inhibitor tuaj yeem muab cov tshuaj kho tshiab rau HBV-Gn. Txawm li cas los xij, qhov tseeb molecular network ntawm HBX hauv tib neeg rTecs tsis to taub tag nrho.(echinacoside los ntawm cistanche)(ecH) yog ib tug natural compound muab rho tawm los ntawmCistanchenroj tsuag, uas qhia tau hais tias antiapoptotic thiab anti-inflammatory teebmeem (15,16). Ib txoj kev tshawb fawb yav dhau los tau tshaj tawm tias ecH induces proliferation thiab tiv thaiv apoptosis ntawm plab hnyuv epithelial hlwb (17). Tsis tas li ntawd, ecH tau tshaj tawm tias yuav ua kom cov pob txha rov tsim dua tshiab los ntawm kev ua kom cov hlwb osteoblast loj tuaj (18). ecH tseem tuaj yeem txo HBV replication, antigen qhia thiab o hauv nas plab hnyuv epithelial hlwb (16,19). Txawm li cas los xij, cov txiaj ntsig lom neeg ntawm ecH ntawm rTecs tsis tau qhia meej meej.
TreM2 overexpression txhawb kev loj hlob ntawm glioma hlwb (22). Los ntawm qhov sib piv, TreM2 knockdown txo qhov kev hloov pauv ntawm nF-κB mus rau lub nucleus hauv degenerative human nucleus pulposus cells (23). Tsis tas li ntawd, TreM2 tau raug txheeb xyuas tias yog lub hom phiaj kho tshiab rau tib neeg intervertebral disc degeneration (23). Txawm li cas los xij, kev ua haujlwm lom neeg ntawm TreM2 hauv tib neeg rTecs tsis tau tshaj tawm. nyob rau hauv txoj kev tshawb no, HBX overexpression (oeHBX) tau induced nyob rau hauv tib neeg rTecs (HK-2 cell kab) thiab tom qab ntawd, cov nyhuv ntawm ecH(echinacoside los ntawm cistanche) ntawm cov kab mob oeHBX tau tshawb xyuas. Lub hom phiaj ntawm txoj kev tshawb fawb tam sim no yog txhawm rau tshawb xyuas cov haujlwm ntawm HBX thiab qhov muaj peev xwm ntawm ecH ua tus neeg saib xyuas zoo rau HBV-Gn.
Khoom siv thiab txoj kev
Cell kab lis kev cai.Tib neeg rTec cell kab HK-2 tau yuav los ntawm Shanghai Yaji Biotechnology co., ltd. HK-2 hlwb raug coj los ntawm DME/F12 media (cat. no. SH30023.01B; Hyclone; cytiva) ntxiv nrog 10 feem pua fetal bovine serum (cat. no. 16000-044; Gibco; Thermo Fisher Scientific, inc .), 2 mM l-glutamine thiab 1% penicillin/streptomycin (cat. no. P1400-100; Beijing Solarbio Science & Technology co., Ltd.) ntawm 37˚C nrog 5% CO2.
RNA muab cais nyob ib leeg thiab thim rov qab transcription-quantitative PCR (RT-qPCR).Tag nrho rna tau muab rho tawm los ntawm HK-2 hlwb siv Trizol® (cat. no. 1596 -026; Invitrogen; Thermo Fisher Scientific, inc.), raws li cov chaw tsim khoom raws tu qauv. Tag Nrho RNA tau thim rov qab rau hauv cDNA siv First-Strand cDNA Synthesis cov khoom siv raws li cov chaw tsim khoom raws tu qauv (cat. no. K1622; Thermo Fisher Scientific, Inc.). qPCR tau ua tiav siv SYBr-Green premix raws li cov chaw tsim khoom raws tu qauv (cat. No. K0223; Thermo Fisher Scientific, Inc.) ntawm ABI-7300 lub sijhawm tiag tiag (Applied Biosystems; Thermo Fisher Scientific, Inc.). Cov xwm txheej ntawm PCR yog: 95˚C rau 10 feeb tom qab 40 lub voj voog ntawm 95˚C rau 15 feeb, 60˚C rau 45 feeb. Peb yuav tsum tau rov ua dua rau txhua qhov kev tshwm sim. Cov khub primer hauv qab no tau siv rau qPCR: HBX rau pem hauv ntej, 5'-GGcTGcTaGGTTGTacTG-3' thiab thim rov qab, 5'-caGaGGTGaaGcGaaGTG -3'; TreM2 rau pem hauv ntej, 5'-TGGcacTcTcaccaTTacG-3' thiab rov qab, 5'-ccTccc aTcaTcTTccTTcac-3'; thiab GaPdH rau pem hauv ntej, 5'-AAT cccaTcaccaTcTTc-3' thiab thim rov qab, 5'-aGGcTGTTG TcaTacTTc-3'. mRNA qib tau suav hais tias siv 2-ΔΔCq txoj kev thiab normalized rau cov gene hauv cov ntaub ntawv.GAPDH (24).
Overexpression thiab poob.Txhawm rau induce overexpression ntawm HBX thiab TreM2, tag nrho-ntev HBX lossis TreM2 cDNA sequences tau muab tso rau hauv plVX-puro vector (cleantech laboratories, inc.) los ntawm kev zom ob zaug (Hindiii thiabEcoRI). Tom qab ntawd, cov plasmid recombined (1.5 µg) tau kis mus rau HK-2 hlwb (2x105). Cov plasmid (ib qho vector khoob, 1 µg) tau hloov pauv mus rau HK-2 hlwb (2x105) raws li kev tswj tsis zoo (oenc) siv lipofectamine® 2000 (cat. no. 11668-027, Invitrogen, Thermo Fisher Scientific, Inc.). ecH(echinacoside los ntawm cistanche)(cat. no. 82854-37-3; Biopurify Phytochemicals, ltd.) tau yaj hauv DMSO (cat. no. d2650; Sigma-Aldrich; Merck KGaa) ntawm qhov concentration ntawm 1, 2.5, 5, 10, 20 thiab
50 mg / l; thiab ntxiv rau kab lis kev cai ntawm transfected oeHBX los yog oeTreM2 hlwb. Qhov kev sim tom ntej pib 48 teev tom qab.
Txhawm rau rhuav tshem TreM2 kev qhia, peb qhov cuam tshuam me me (si)RNAs (siTreM2-1, siTreM2-2 thiab siTreM2-3; 20 µM) targeting TreM2 tau ua ke (Shanghai Majorbio Bio-Pharm Technology co. . ltd.) thiab tom qab ntawd kis mus rau HK-2 hlwb (2x105) siv lipofectamine® 2000 raws li cov chaw tsim khoom raws tu qauv (Invitrogen; Thermo Fisher Scientific, Inc.). Ib qho tsis tshwj xeeb scrambled siRNA ib ntus (5'uucccGaacGuGucacGu3, 25 nM) si-negative control (nc) tau siv los ua qhov kev tswj tsis zoo. Lub hom phiaj qhov chaw thiab cov kab ke ntawm TreM2 sirnas tau muab rau hauv Table Si. Qhov kev sim tom ntej tau ua tiav 48 teev tom qab.
Western blotting.Tag nrho cov protein tau muab rho tawm los ntawm HK-2 hlwb
siv RIPA lysis buffer (cat. no. BYl40825; Jrdun Biotech Co., Ltd.). Tag nrho cov protein tau suav nrog siv cov khoom siv Bicinchoninic Acid assay (cat. no. PICPI23223; Thermo Fisher Scientific, inc.) raws li cov chaw tsim khoom raws tu qauv thiab 20 µg protein / txoj kab raug cais ntawm SDS-PaGe ntawm 15 feem pua gel. Cov densitometry ntawm cov qauv tau txiav txim siab siv tus nyeem ntawv microplate (dnM-9602, Pulangxin). Tom qab ntawd, cov protein sib cais tau xa mus rau PVDF daim nyias nyias. Tom qab thaiv nrog 5 feem pua ntawm cov mis nyuj qhuav tsis muaj rog rau 1 teev ntawm chav tsev kub, daim nyias nyias tau tsim nrog thawj cov tshuaj tiv thaiv (Table SII) ntawm 4˚C thaum hmo ntuj thiab rov ua dua nrog cov tshuaj tiv thaiv thib ob los tiv thaiv nas igG (1: 1, 000, cat. no. a0216, Beyotime Institute of Biotechnology) rau 1 teev ntawm 37˚C. Cov kab mob immunoreactive protein tau pom los ntawm kev siv ecl system (cytiva). Blots tau ua nyob rau hauv triplicate.GAPDHthiab H3 tau siv los ua kev tswj hwm kev thauj khoom rau cytoplasmic thiab nuclear proteins, feem.
Cov txiaj ntsig
ECH (echinacoside los ntawm cistanche)suppresses txoj haujlwm ntawm HBX hauv HK-2 hlwb.Ntsuam xyuas
Kev ua haujlwm ntawm HBX, HBX overexpression raug ntxias hauv HK-2 hlwb. Cov txheeb ze mrna thiab cov protein ntau ntawm HBX tau nce siab hauv oeHBX hlwb piv nrog oenc hlwb (Fig. 1a thiab B). Tom qab ntawd, oeHBX hlwb raug coj los ntawm ntau qhov sib txawv ntawm ecH (1, 2.5, 5, 10, 20 thiab 50 mg / l; e1, e2.5, e5, e10, e20 thiab e50, feem). HBX overexpression txo qhov kev loj hlob ntawm HK-2 hlwb, thiab qhov kev txo qis no tau thim rov qab los ntawm ecH nyob rau hauv cov koob tshuaj ntawm 24 thiab 48 h (Fig. 1c).
Tsis tas li ntawd, qhov kev loj hlob ntawm oeHBX hlwb tsis muaj qhov sib txawv tseem ceeb piv nrog E1-kho hlwb (Fig. 1c). Los ntawm qhov sib piv, e10 kev kho mob tau nce qhov kev loj hlob ntawm oeHBX hlwb piv nrog E20 thiab E50 kev kho mob uas tsis muaj qhov sib txawv tseem ceeb (Fig. 1c). Yog li, cov txiaj ntsig ntawm ecH ntawm apoptosis tau tshuaj xyuas hauv e2.5, e5 thiab e10- kho cov hlwb. HBX over-expression ho nce apoptosis ntawm HK-2 hlwb, thiab apoptosis tus nqi ntawm oeHBX hlwb txo nrog ecH kev kho mob raws li koob tshuaj raws li (Daim duab 1d). zuag qhia tag nrho, cov txiaj ntsig tau qhia tias ecH inhibited kev ua haujlwm ntawm HBX hauv HK-2 hlwb nyob rau hauv koob tshuaj.
TREM 2 kev qhia yog inhibited los ntawm ECH(echinacoside los ntawm cistanche) hauv kis tau oeHBX ua
hlwb.rT-qPcr thiab western blotting tau siv los tshuaj xyuas cov txheeb ze mrna thiab protein qhia theem ntawm TreM2 hauv oeHBX hlwb, raws li. TreM2 mrna thiab cov protein qhia qib tau nce qib hauv oeHBX hlwb piv nrog oenc hlwb (Fig. 2a thiab B). Txawm li cas los xij, ecH txo qis cov kev qhia theem ntawm TreM2 hauv cov kab mob oeHBX hloov pauv raws li kev siv tshuaj (Daim duab 2a thiab B). Yog li, cov txiaj ntsig tau qhia tias HBX qhia tau zoo cuam tshuam nrog TreM2 kev qhia, thiab qhia ntxiv txog kev cuam tshuam ntawm ecH ntawm HBX hauv HK-2 hlwb.
Npog thiab overexpression ntawm TREM 2 hauv HK-2 hlwb.Txhawm rau ntsuas qhov ua haujlwm ntawm TreM2, TreM2 knockdown thiab overexpression tau raug ntxias hauv HK-2 hlwb siv rna cuam tshuam thiab lentiviral vector, feem. Rau qhov kev ntsuam xyuas knock-down, peb siRNAs tsom rau tib neeg cov noobTREM 2(siTreM2-1, siTreM2-2 thiab siTreM2-3) tau kis mus rau HK-2 hlwb, thiab ib qho tsis tshwj xeeb siRNA tau siv los ua kev tswj tsis zoo (sinc). tag nrho peb TreM2 sirnas tau ua tiav qhov kev qhia endogenous ntawm TreM2 hauv HK-2 hlwb (Fig. 3a thiab B). Txawm li cas los xij, cov txheeb ze qis tshaj plaws TreM2 mrna thiab qib qhia protein tau pom hauv siTreM2-1 thiab siTreM2-2- cov hlwb hloov pauv (Daim duab 3a thiab B), yog li, siTreM2-1 thiab siTreM{{13 }}hloov cov hlwb raug xaiv rau kev sim tom ntej. Rau qhov kev sim ntau dhau, lub plasmid uas muaj tag nrho-ntev tib neeg TreM2cdna ib ntus tau tsim thiab tom qab ntawd hloov mus rau HK-2 hlwb (oeTreM2). a
mock plasmid tau txais kev tswj tsis zoo (oenc). Qib ntawm TREM2 qhia tau nce ntau hauv oeTREM2 hlwb piv nrog oenc hlwb (Fig. 3c thiab d). Yog li ntawd, oeTreM2 hlwb tau siv rau kev sim tom ntej.
TREM 2 ntsiag to txo tus apoptosis ntawm oeHBX ua hlwb.Cov apoptosis profile ntawm oeHBX hlwb hloov nrog siTREM2 los yog sinc raug soj ntsuam. Tus apoptosis tus nqi ntawm oeHBX ntxiv rau cov hlwb tau ntau dua piv nrog cov hlwb qhib. Txawm li cas los xij, tus nqi apoptosis tau txo qis hauv oeHBX ntxiv rau siTreM2-1 lossis siTreM2-2 hlwb piv nrog oeHBX plus sinc hlwb (Fig. 4a). Cov txiaj ntsig tau qhia tias TreM2 knockdown inhibited kev ua haujlwm ntawm HBX thaum HK-2 cell apoptosis.
Survivin belongs rau inhibitor ntawm tsev neeg apoptosis protein, uas inhibits apoptotic kev ua si thiab suppresses cell tuag (25). Targeting Survivin tau raug txheeb xyuas tias yog ib txoj hauv kev tshiab rau kev kho mob raum cell carcinoma (26). nF-κB kuj yog ib qho apoptosis inhibitor uas ua lub luag haujlwm hauv cov txheej txheem antiapoptotic qog (27). Tsis tas li ntawd, caspase3 ua kom muaj kev sib raug zoo nrog apoptosis (28). Hauv txoj kev tshawb fawb tam sim no, cov ntsiab lus protein ntawm TreM2, Survivin thiab cleaved caspase3 hauv HK-2 hlwb raug xam. Qib ntawm TREM2 qhia tau txo qis hauv oeHBX ntxiv rau siTreM{10}}/2 hlwb piv nrog oeHBX ntxiv rau cov hlwb (Fig. 4B). Qib ntawm Survivin qhia tau nce ntau hauv oeHBX ntxiv rau siTreM2-1/2 hlwb piv nrog oeHBX hlwb. Tsis tas li ntawd, theem ntawm cleaved caspase3 qhia tau txo qis hauv oeHBX ntxiv rau siTreM2-1/2 hlwb piv nrog oeHBX plus sinc hlwb (Fig. 4B). Tsis tas li ntawd, oeHBX txo qis kev hloov pauv ntawm NF-κB mus rau lub nucleus, thiab siTREM2-1/2 transfection ua rau nce nF-κB nuclear translocation (Fig. 4B). Ua ke, cov txiaj ntsig tau qhia tias TreM2 yog qhov qis qis ntawm HBX hauv HK-2 hlwb, yog li, HBX tuaj yeem txhawb nqa apoptosis los ntawm kev tswj hwm TreM2 qhia hauv tib neeg rTecs.
TREM 2 overexpression suppresses tus kev hloov chaw ntawmNF-κB rau tus nucleus hauv HK-2 hlwb.Cov nyhuv ntawm ecH(echinacoside los ntawm cistanche)ntawm oeTreM2-cov hlwb hloov tau raug tshuaj xyuas. TreM2 overexpression txhawb lub apoptosis ntawm HK-2 hlwb (Fig. 5a). Lub apoptosis ntawm oeTREM2 hlwb tau txo qis los ntawm kev kho ECH (E10; Fig. 5A). Tsis tas li ntawd, ECH txo qis kev qhia ntawm TreM2 hauv oeTreM2 hlwb. TREM2 overexpression txo qis qhov kev qhia theem ntawm Survivin, txawm li cas los xij, qhov kev txo qis hauv kev qhia tau thim rov qab los ntawm ecH. Tsis tas li ntawd, cov protein qhia theem ntawm cleaved caspase3 tau nce ntau hauv oeTreM2 hlwb piv nrog oenc hlwb; ib qho kev cuam tshuam uas tau txo qis los ntawm kev kho ECH. Tsis tas li ntawd, ecH txhawb kev hloov pauv ntawm nF-κB mus rau lub nucleus hauv oeTreM2 hlwb (Fig. 5B). Ua ke, cov txiaj ntsig tau qhia tias ecH kuj tseem cuam tshuam txoj haujlwm ntawm TreM2 hauv tib neeg rTec hlwb.
HBXfunctions yog tuav los ntawm tus NF-κB inhibitor PDTChauv tib neeg RTECs.Txhawm rau txheeb xyuas qhov kev sib raug zoo ntawm
HBX thiab nF-κB, HK-2 hlwb tau coj los ua ke nrog ib qho tshwj xeeb nF-κB inhibitor, PdTc (10 µmol / l; P10). Lub cell apoptosis tus nqi ntawm oeHBX hlwb tau nce ntau dua piv nrog oenc hlwb (Fig. 6a). Txawm li cas los xij, oeHBX ntxiv rau PdTc hlwb tau pom qhov nce apoptosis ntau dua piv nrog oeHBX hlwb. Tsis tas li ntawd, cov txheeb ze mRNA thiab protein qhia theem ntawm TreM2 tau txo qis hauv oeHBX ntxiv rau PdTc hlwb piv nrog oeHBX hlwb (Fig. 6B). Yog li ntawd, cov txiaj ntsig
qhia tias nF-κB tsis zoo tswj TreM2 qhia hauv oeHBX-hloov hlwb.
NF-κB inhibitor PDTC suppresses TREM 2 txhawb nqa kev ua si hauv oeHBX ua hlwb.ib tus neeg tshaj xov xwm luciferase (pGl3-enhancer-luc2) uas muaj cov tsiaj qus-hom kev txhawb nqa ib ntus ntawm TreM2 (pGl3-enhancer-luc2-}pTreM2) tau tsim thiab tom qab ntawd hloov mus rau hauv oenc , oeHBX thiab oeHBX ntxiv rau P10 kab lis kev cai.
Cov kev ua luciferase ntawm tus neeg sau xov xwm vector uas muaj cov tsiaj qus-hom TREM2 txhawb nqa tau nce ntau hauv oeHBX hlwb piv nrog oenc hlwb. Txawm li cas los xij, PdTc cuam tshuam qhov kev ua haujlwm ntawm luciferase ntawm tus neeg sau xov xwm hauv oeHBX hlwb (Fig. 7). zuag qhia tag nrho, cov txiaj ntsig tau qhia tias PdTc inhibited qhov kev hloov pauv ntawm TreM2 los ntawm kev tawm tsam kev txhawb nqa ntawm TreM2 hauv oeHBX hlwb.
Kev sib tham
HBX feem ntau yog qhia hauv rTecs ntawm cov neeg mob HBV-Gn, thiab ua haujlwm raws li kev txiav txim siab ntawm tus kab mob kis (11,29). Yog li ntawd, kev paub txog kev ua haujlwm ntawm HBX molecule network yog ib kauj ruam tseem ceeb hauv kev tsim kho tshiab rau kev kho HBV-Gn. Lub hom phiaj ntawm txoj kev tshawb fawb tam sim no yog txhawm rau tshuaj xyuas ntxiv txog kev ua haujlwm ntawm HBX thiab tshawb nrhiav nws lub peev xwm molecular network hauv tib neeg rTecs.
HBX inhibits kev loj hlob ntawm rTecs (11). nyob rau hauv txoj kev tshawb no tam sim no, antiproliferation thiab pro-apoptosis functions ntawm HBX nyob rau hauv tib neeg RTECs tau txheeb xyuas, qhia tias HBX suppressed txoj kev loj hlob ntawm tib neeg rTecs.a yav dhau los txoj kev tshawb no qhia tias ecH.(echinacoside los ntawm cistanche)inhibits HBV replication thiab antigen qhia (19). hauv kev tshawb fawb tam sim no, ecH(echinacoside los ntawm cistanche)Kev kho mob cuam tshuam txoj haujlwm ntawm HBX hauv HK-2 hlwb, yog li, HBX tuaj yeem cuam tshuam los ntawm ecH hauv HK-2 hlwb.
Molecular Medicine rePorTS 22: 1137-1144, 2020 1143
Tsis tas li ntawd, cov txiaj ntsig tau pom tias ecH(echinacoside los ntawm cistanche)tuaj yeem ua tus neeg sawv cev kho mob rau HBV-Gn.
TreM2 yog ib qho kev tiv thaiv kab mob hauv lub cev uas ua lub luag haujlwm hauv cov lus teb inflammatory (30). Nyob rau hauv txoj kev tshawb no, HBX qhia tau zoo txuam nrog TreM2 qhia hauv tib neeg RTECS. Ntxiv mus, TREM2 knockdown txo qis tus nqi apoptosis ntawm oeHBX hlwb, thiab ecH.(echinacoside los ntawm cistanche)Kev kho mob txo cov nyhuv ntawm oeTreM2 ntawm cell apoptosis. Ua ke, cov txiaj ntsig no tau qhia tias TreM2 tau tsom los ntawm HBX hauv HK-2 hlwb. Yog li ntawd, ecH(echinacoside los ntawm cistanche)tuaj yeem cuam tshuam cov apoptosis ntawm tib neeg rTecs los ntawm kev thaiv kev ua haujlwm ntawm HBX / TreM2 teeb liab txoj hauv kev.
Ib daim ntawv tshaj tawm dhau los tau pom tias nF-κB, tsis yog tsuas yog ua lub luag haujlwm hauv cell apoptosis tab sis kuj tseem koom nrog kev tswj hwm kev tiv thaiv kab mob thiab kev mob (31). Tsis tas li ntawd, TreM2 yog kho los ntawm nF-κB-sensitive microRNA-34a thaum lub sij hawm Alzheimer's kab mob thiab macular degeneration (32,33). nyob rau hauv txoj kev tshawb no tam sim no, tus nqi apoptotic ntawm oeHBX hlwb tau nce ntxiv nyob rau hauv lub xub ntiag ntawm PdTc. Rau qhov zoo tshaj plaws ntawm peb txoj kev paub, txoj kev tshawb fawb tam sim no tau qhia thawj zaug tias, NF-κB inhibitor PdTc tau txwv tsis pub cov kev txhawb nqa ntawm TreM2. Tsis tas li ntawd, cov txiaj ntsig tau qhia tias TreM2 tsis zoo tswj kev hloov pauv ntawm nF-κB mus rau lub nucleus hauv HK-2 hlwb, tab sis tau cuam tshuam zoo nrog cleaved caspase3 qhia qib. TreM2 ua lub luag haujlwm sib txawv hauv HK-2 hlwb rau nws lub luag haujlwm hauv tib neeg degenerative nucleus pulposus thiab glioma hlwb (22,23). Yog li, txoj kev tshawb fawb tam sim no tau qhia tias TreM2 yuav muaj cov haujlwm sib txawv hauv ntau hom tib neeg lub hlwb.
Ua ke, txoj kev tshawb fawb tam sim no, tsis yog tsuas yog qhia tias nF-κB yog ib qho tshiab ntawm HBX / TreM2 signaling pathway tab sis kuj qhia tias nF-κB tsis zoo tswj hwm TreM2 kev qhia hauv tib neeg rTecs. Txawm li cas los xij, cov kev txwv loj ntawm kev tshawb fawb tam sim no yog qhov tsis muajhauv vivokev sim thiab cov ntaub ntawv kho mob. Yog li ntawd, ntxivhauv vivothiab cov kev tshawb fawb soj ntsuam yuav tsum tau lees paub qhov kev tshawb pom ntawm qhov kev tshawb fawb tam sim no.
Hauv kev tshawb fawb tam sim no, kev ua haujlwm ntawm ecH(echinacoside los ntawm cistanche)tau tshawb xyuas thiab cov txiaj ntsig tau pom tias muaj peev xwm cuam tshuam ntawm ecH(echinacoside los ntawm cistanche)ntawm txoj kev taw qhia hauv tib neeg rTecs. Tsis tas li ntawd, txoj kev tshawb fawb tam sim no tau txhim kho cov kev paub uas twb muaj lawm ntawm kev ua haujlwm lom neeg ntawm ecH hauv tib neeg rTec hlwb thiab tseem qhia nws lub peev xwm ua tus neeg sawv cev kho tshiab rau HBV-Gn.
Cov ntaub ntawv
1. Karayiannis P: Tus kab mob siab B: virology, molecular biology, lub neej voj voog, thiab intrahepatic kis. Hepatology thoob ntiaj teb 11: 1-9, 2017.
2. Seeger c thiab Mason WS: Kab mob siab B virus biology. Microbiol Mol Biol rev 64: 51-68, 2000.
3. Usama e , ana Maria S, W ray K thiab Fervenza Fc: Kev kho kab mob siab B virus-associated nephropathy. nephron clin Pract 119: c41-c49, 2011.
4. Zhang Y, li J, Peng W, Yu G, Wang l, chen J thiab Zheng F: HBV-associated Postinfectious acute Glomerulonephritis: ib daim ntawv qhia txog 10 tus neeg mob. PloS ib 11: e0160626, 2016.
5. Slagle Bl thiab Bouchard MJ: Kab mob siab B Virus X thiab kev cai ntawm Viral Gene qhia. txias caij nplooj ntoos hlav Harb Perspect Med 6: a021402, 2016.
6. Guerrieri F, Belloni l, d'andrea d, Pediconi n, le Pera l, Testoni B, Scisciani c, Floriot o, Zoulim F, Tramontano a,thiab al: Kev txheeb xyuas dav dav ntawm cov hom phiaj HBx genomic ncaj qha. BMc genomics 18: 184, 2017.
7. Shi T, Hua Q, Ma Z thiab lv Q: downregulation of mir-200a-3p induced los ntawm kab mob siab B tus kab mob siab B X (HBx) protein txhawb nqa cell proliferation thiab invasion nyob rau hauv HBV-kis kab mob hepato-carcinoma. Pathol res Pract 213: 1464-1469, 2017.
8. Tian Y, Xiao X, Gong X, Peng F, Xu Y, Jiang Y thiab Gong G: HBx txhawb kev loj hlob ntawm tes los ntawm kev cuam tshuam kev sib tham ntawm mir-181a thiab PTen. Sci rep 7:40089, 2017.
9. Idris Me, Hachem H, Koering c, Merle P, Thénoz M, Montreux F, thiab Wattel e: HBx ua rau cellular senescence los yog cell proliferation nyob ntawm cellular phenotype. J Viral Hepat 23: 130-138, 2016.
10. Wang X, Wang l, Zhu n, Zhou Y, Gu lJ thiab Yuan WJ: Kab mob siab B kab mob X protein modulates raum tubular epithelial cell-induced T-cell thiab macrophage teb. Immunol cell Biool 94: 266-273, 2016.
11. He P, Zhang d, li H, Yang X, li d, Zhai Y, Ma l thiab Feng G: kab mob siab B virus X protein modulates apoptosis nyob rau hauv tib neeg lub raum proximal tubular epithelial hlwb los ntawm activating lub JaK2/STaT3 signaling pathway. int J Mol Med 31: 1017-1029, 2013.
12. Yang Y, Wang X, Zhang Y thiab Yuan W: Kab mob siab B kab mob X protein thiab proinflammatory cytokines synergize los txhim kho Trail-induced apoptosis ntawm lub raum tubular hlwb los ntawm upregulation ntawm dr4. int J Biochem cell Biool 97: 62-72, 2018.
13. He P, Zhou G, Qu d, Zhang B, Wang Y thiab li d: HBx inhibits proliferation thiab induces apoptosis ntawm Fas/Fasl upregulation nyob rau hauv nas lub raum tubular epithelial hlwb. J nephrol 26: 1033, 2013.
14. Han W, luo M, He M, Zhu Y, Zhong Y, ding H, Hu G, liu l, chen Q thiab lu Y: HBx gene transfection cuam tshuam lub voj voog ntawm thawj lub raum tubular epithelial hlwb los ntawm regulating cyclin qhia. Mol Med rep 18: 1947-1954, 2018.
