Characteristics Of Core Fucosylation Of Pericytes During Renal Interstitial Fibrosis

Background: CKD(Chronic Kidney Disease)is an irreversible disease with high morbidity and mortality which effects over 10% of general population.RIF(Renal Interstitial Fibrosis)is widely known as a common pathological change of CKD.Pericytes were recently found as a major contributor of myofibroblast which can directly cause fibrosis.The special location determines that pericytes fulfill a function of mediator under normal condition or be an initiator of fibrosis under abnormal condition.There are cross-talks existing among pericytes,endothelial cells,and epithelial cells,such as TGF,PDGF,and VEGF pathway.These pathways are highly related to RIF.However,single blocking of one involved pathway is not enough to hold the whole process of RIF.Objective: Our and others' research have found that TGF?R,PDGFR,and VEGFR are modified by core fucose,and Fut8 is a crucial enzyme of the modified process.Our research focused on whether core fucosylation regulates pericyte-myofibroblast transition.Methods: According to different OXFORD classification,we collected 32 Ig AN patients to observe their change of core fucosylation level.Further,UUO1 d,3d,7d mice model were administered to observe core fucosylation change during renal fibrosis in vivo,and FACS or MACS were applied for primary mouse pericytes isolation and pericytes-myofibroblast transition in vitro model was established to observe core fucosylation change.Results: Our research found that core fucosylation level of CKD patients were indeed gradually elevated along with developing of disease period and the severe extent of pericyte detachment and pericyte-myofibroblast transition also increased along with disease progress.Consistently,similar phenomenon was observed in animal models and in vitro study.Furthermore,we used Fut8 shRNA and Fut8 siRNA to knock down Fut8 in vivo or in vitro,interestingly,we found that inhibition of core fucosylation can obviously alleviate RIF and prevent pericyte-myofibroblast transition in vivo and in vitro.Conclusion: we found that core fucosylation play a vital role in pericyte activation during RIF.And this founding may be a novel potential therapeutic target of RIF from a glycosylation perspective.