Ntu 1: Cannabinoid Receptor Hom 2 Txhawb rau lub raum Fibrosis Los ntawm Orchestrating -catenin Signaling

Hu rau: emily.li@wecistanche.com

Shan Zhou, et al

State Key Laboratory ntawm Organ Failure Research, National Clinical Research Center ofLub raumKab mob, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China;' Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China;>Department of Nephrology, Huadu District People's Hospital, Southern Medical University, Guangzhou, Suav; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; thiab Bioland Laboratory (Guangzhou Regenerative Medicine thiab Health, Guangdong Laboratory), Guangzhou. Tuam Tshoj

Lub endocannabinoid system muaj ntau yam teebmeem. Los ntawm kev cuam tshuam nrog cannabinoid receptor hom 1 thiab hom 2, qhov system no tuaj yeem cuam tshuam rau kev loj hlob ntawm tus kab mob.

Cistanche tuaj yeem kho mob raum

Yav dhau los, peb tau pom tias qhib tau cannabinoid receptor hom 2 (CB2) khoraumfibrosis. Txawm li cas los xij, lub hauv paus mechanisms tseem tsis tau txiav txim siab. Ntawm no, peb tshaj tawm tias CB2 tau tswj hwm feem ntau hauvraumcevepithelial hlwb nyob rau hauv unilateral urinary obstruction thiab ischemia-reperfusion raug mob qauv nyob rau hauv nas, thiab nyob rau hauv cov neeg mob uas muaj ntau yam ntawmraumkab mob. CB2 qhia tau zoo sib xws nrog rau kev loj hlob ntawm lub raum fibrosis thiab nrog rau kev ua kom -catenin.

Tsis tas li ntawd, CB2 induced tsim ib tug -arrestin 1 / Src / -catenin complex, uas ntxiv ua rau lub nuclear translocation ntawm -catenin thiab ua rau fibrotic raug mob. Incubation nrog XL-001, ib qho inverse agonist rau CB2, los yog knockdown ntawm -arrestin 1 inhibited CB2- ua rau ua rau -catenin thiab fibrotic raug mob. Tshwj xeeb, CB2 potentiated Wnt{12}}induced -arrestin 1/ -catenin activation thiab augmented lub pathogenesis ntawmraumfibrosisnyob rau hauv nas nrog unilateral ischemia-reperfusion raug mob los yog folic acid-induced nephropathy. Knockdown ntawm -arrestin 1 inhibited CB2 agonist AM 1241-induced -catenin activation thiabraumfibrosis. Los ntawm kev txhawb nqa kev soj ntsuam ib ntus, putative transcription factor binding sites for T-cell factor/lymphoid enhancer factor tau pom nyob rau hauv cov cheeb tsam txhawb nqa ntawm CB2 noob tsis hais hom twg. Kev nthuav tawm ntau dhau ntawm -catenin ua rau muaj kev sib txuas ntawm T-cell factor / lymphoid enhancer factor-1 rau cov chaw no, txhawb nqa qhov kev qhia ntawm CB2, -arrestin 1, thiab proto-oncogene Src, thiab ua rau lawv tsub zuj zuj. Yog li, CB2 / -catenin txoj hauv kev zoo nkaus li tsim kom muaj kev sib txuas lus ua kom rov ua haujlwm lub voj voog uas ua lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob.raumfibrosis.

Lus Txhais Lus

Cannabinoid receptors koom nrog hauv cov ntaub so ntswg fibrosis. Txawm hais tias cannabinoid receptor type 1 activation tau raug tshaj tawm los kho lub raum fibrosis, lub luag haujlwm ntawm cannabinoid receptor type 2 (CB2) tseem yuav tsum tau ua kom nthuav dav. Txoj kev tshawb no muab pov thawj rau lub luag haujlwm tsis zoo ntawm CB2 hauv cov kab mob ntawm lub raum fibrosis. Cov kev tshawb pom qhia txog qhov tshiab CB2 / -catenin txoj hauv kev uas txhawb nqa lub raum fibrosis. Blockade ntawm CB2 yog qhov muaj peev xwm kho tau los tiv thaiv lub raum fibrosis hauv ntau hom nephropathies. Cov kev tshawb pom tseem muab cov lus ceeb toom txog kev noj qab haus huv rau cov pab pawg loj hlob sai ntawm cov neeg siv khoom endocannabinoid, rau ob qho tib si ua si thiab tshuaj kho mob.

Cov kab ke endocannabinoid ua lub luag haujlwm tseem ceeb hauv cov hlab plawv, neurodegenerative, thiab cov kab mob metabolic.-Los ntawm kev cuam tshuam nrog cannabinoid receptors hom 1 (CB1) thiab hom 2 (CB2), cov kab mob endocannabinoid kuj tseem tuaj yeem cuam tshuam cov kev mob tshwm sim.raumkab mob. CB1 plays lub luag haujlwm tsis zoo hauv lub raum fibrosis.-Txawm li cas los xij, lub luag haujlwm ntawm CB2 hauv lub raum fibrosis tseem tsis pom.

CB2 yav dhau los tau tshaj tawm tias tau koom nrog hauv lub cev tiv thaiv kab mob. "Tsis ntev los no, CB2 tau pom tias tau hais tawm hauv kid-neys.5,1-1 Hauv cov ntshav qab zib nephropathy thiab podocytes thaum ntxov, CB2 plays lub luag haujlwm tiv thaiv hauv cellular. Nyob rau hauv fibrotic raug mob, CB2 yog upregulated nyob rau hauv tubular hlwb thiab koom nyob rau hauv fibrogenic cov lus teb, raws li qhia nyob rau hauv peb ua hauj lwm yav dhau los. CB2 kuj qhia nyob rau hauv interstitial fibroblasts thiab macrophages thiab kho kom haum lawv ua kom. (2-AG), lub ntsiab endogenous ligand ntawm CB2, kuj nce nyob rau hauv obstructivelub raum. Txawm hais tias ib qho kev tshawb fawb dhau los tau taw qhia tias qhov ua kom

Daim duab 1|Cannabinoid receptor type 2 (CB2) yog lub sij hawm-dependently induced nyob rau hauv lub raum raug mob thiab txuam nrog fibrogenesis. (a) Cov neeg sawv cev micrographs qhia CB2 qhia thiab collagen deposition hauv ob lub raum tom qab ischemia-reperfusion raug mob (IRl). IRI phais tau ua nyob rau hauv nas, thiab nas tau txi ntawm lub sij hawm taw qhia. Cryosections tau raug fluorescence nyob rau hauv situ hybridization (FISH) staining rau CB2 (sab saum toj), thiab parattin seem tau subiected rau Masson's trichrome staining rau collagen deposition (hauv qab). Xub qhia qhov zoo staining.Rau CB2 FISH staining, bar =75 um; rau Masson's trichrome staining, bar=50 um.(b,C) Kab rov tav reqression qhia lub raum CB2 muaj kev cuam tshuam zoo nrog rau qhov ntawm fibrosis lossis neutrophil gelatinase-associated lipocalin (NGAL) qhia hauv IRl nas qauv. Cov nas tau txi ntawm 3 lossis 7 hnub tom qab IRI. Lub raum mRNA qib ntawm CB2 thiab NGAL raug soj ntsuam los ntawm ntau yam polymerase saw cov tshuaj tiv thaiv.raumfibrosis tau txheeb xyuas los ntawm qhov ntau ntawm Masson's trichrome staining. Spearman correlation coefficient (Rs) thiab P tus nqi yog qhia. (dg) Tus neeg sawv cev Western blot thiab ntau cov ntaub ntawv qhia lub raum qhia ntawm fibronectin, g-smooth leeg actin (SMA), thiab lub raum raug mob molecule-1 (Kim-1) ntawm lub sijhawm taw qhia tom qab IRl. Cov naj npawb (1-3) qhia txhua tus tsiaj hauv ib pab pawg aiven.**P<0.01 versus="" the="" sham="" control="" group;=""><><0.001 versus="" the="" iri="" 3d="" group="" (n="5-6).">