GSE161737
CD47 modulates the interaction of ?-catenin with E-cadherin and participates in epithelial–mesenchymal transformation in lipid nephrotoxicity
Hyperlipidemia, an important risk factor for cardiovascular diseases and end-stage renal disease, often increases renal injury and compromises kidney function. In the present study, the kidney histology analysis in human samples showed that high lipid levels induced renal fibrosis. However, the mechanism of lipid nephrotoxicity remains unknown. We employed mice models of two kinds to further experiments. The kidney histology analysis in mouse showed that high lipid levels induced renal fibrosis that was further confirmed by Western blot and real-time PCR of fibrotic indexes (fibronection, collagenI and a-SMA). In Vitro analysis also supported that OX-LDL significantly induced fibrotic response in HK-2 tubular epithelial cells. To further ascertain the mechanism of high lipid-induced fibrosis, RNA-sequencing (RNA-Seq) was performed. Combined the Gene Ontology (GO) analysis results of differentially expressed mRNAs obtained by RNA-Seq with the results of LC-MS/MS and STRING Functional Association Networks showed that CD47 modulated the interaction of ?-catenin with E-cadherin and participated in epithelial–mesenchymal transformation in lipid nephrotoxicity. The inhibition of CD47 expression by transfected with shRNA plasmid or treated with anti-CD47 antibody in OX-LDL-treated tubular epithelial cells restored the expression of E-cadherin and attenuated renal injury including fibrosis and inflammatory response. These findings indicate that CD47 may be a therapeutic potential target for long-term lipid abuse-induced kidney injury. Overall design: mRNA profiles of HK-2 cells treated with control and OX-LDL stimulation.