Long Noncoding RNA uc.412 Promotes Mesangial Cell Fibrosis via Binding ELAVL1 in Glomerulosclerosis

Abstract Background: Glomerulosclerosis is a characteristic pathologic feature in chronic kidney disease (CKD). Convincing evidence indicates that the mesangial cells (MCs) play critical role in this process. However, the exact mechanism remains unclear. Using RNA-seq analysis, we previously found that lncRNA uc.412 was involved in the MC proliferation. Here, the effect of uc.412 on glomerular fibrosis and the potential mechanism were explored. Methods: In vivo, CKD mice models were established by 5/6 nephrectomy. The expression of lncRNA uc.412 in CKD was detected by Real-Time PCR. In vitro, MCs were intervened with TGF-β1 (10ng/mL). The uc.412 expression in MCs was detected by in site hybridization. MCs were transfected with uc.412 siRNA or a lentivirus targeting uc.412 and then examined using western blot, Real-Time PCR, RNA pull down assay and immunofluorescence staining. Results: We found that the expression of uc.412 was significantly increased in CKD mice and is induced by TGF-β1 via Smad3- dependent signal pathway. Overexpressing uc.412 caused MCs fibrosis and knockdown of uc.412 alleviated TGF-β1-induced MCs fibrosis. Using RNA pull down analysis, we found that the ELAVL1 was the specific binding protein for uc.412. Moreover, ELAVL1 expression was increased in TGF-β1-treated MCs and silencing ELAVL1 expression attenuated MCs fibrosis. Conclusions: Thus, here, we demonstrated that uc.412, which is regulated in a Smad3-dependent mechanism, is significantly increased during progression of CKD via regulating ELAVL1 expression. Our findings provided the therapeutic strategy for treatment of CKD.