title: AngiotensinII induces HuR shuttling by post-transcriptional regulated CyclinD1 in human mesangial cells.
abstract: Abnormal proliferation of human mesangial cells was the earliest pathological character in chronic kidney disease and linked to the accumulation of extracellular matrix and glomerular sclerosis. Multifunctional Angiotensin (AngII) had been emerged as a key player in initiation and progression of fibrogenic processes in kidney. In mesangial cells, treatment with the proliferation stimulus AngII triggered the escalated cyclinD1 expression, where its association with HuR increased dramatically. In our study, it was demonstrated that both in vivo and in vitro HuR redistribution in dysregulated mesangial cell proliferation accompanied by an abundant cyclinD1 expression following the AngII treatment. ActinomycinD experiments revealed that AngII stabilized cyclinD1 mRNA in human mesangial cells via HuR. Furthermore, employing the RIP-Chip assay yielded cyclinD1 mRNA with a higher affinity to HuR in mesangial cells induced by AngII compared with the normal ones in vitro study. Analysis of a cyclinD1 mRNA directly implicated HuR in regulating cyclinD1 production: cyclinD1 translation increased in HuR-shuttling cells induced by AngII and declined in cells in which HuR levels were lowered by RNA interference. We proposed that the release of HuR-bound mRNAs via an AngII-cyclinD1-HuR regulatory axis was implicated in the evolution of proliferative kidney diseases, providing us a novel therapeutic strategy to treat glomerular disease.
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jingwu Road No. 324, Jinan City, 250021, Shandong, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Che
authors.forename: Liu
authors.initials: L
authors.lastname: Yi
authors.forename: Javed
authors.initials: J
authors.lastname: Akhtar
authors.forename: Chen
authors.initials: C
authors.lastname: Bing
authors.forename: Zhang
authors.initials: Z
authors.lastname: Ruiyu
authors.forename: Wan
authors.initials: W
authors.lastname: Qiang
authors.forename: Wang
authors.initials: W
authors.lastname: Rong
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D050527:Mesangial Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics
chemical_list: C530104:CCND1 protein, human; D051959:ELAV Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000804:Angiotensin II; D019938:Cyclin D1