title: GLIPR-2 overexpression in HK-2 cells promotes cell EMT and migration through ERK1/2 activation.
abstract: The epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells in the adult kidney is one of the key events in renal interstitial fibrosis. Glioma pathogenesis related-2 (GLIPR-2) has been shown to be up-regulated in proximal tubular cells (PTCs) in the fibrotic kidney. However, the biological function of GLIPR-2 remains unknown. In this study, we found that GLIPR-2 expression is elevated in the kidney tissue samples of patients with diabetic nephropathy (DN). Human proximal renal tubular epithelial cells (HK-2 cells) were transfected with pcDNA3.0-GLIPR-2 and selected with G418. To identify the biological function of GLIPR-2, an epithelial-to-mesenchymal transition (EMT) PCR array analysis was performed, and genes that had statistically significantly altered expression levels with more than a two-fold difference compared with the pcDNA3.0-transfected HK-2 cells were considered. Key elements of the EMT process, such as E-cadherin and vimentin, were transcriptionally activated in the pcDNA3.0-GLIPR-2-transfected sublines. In addition, α-SMA gene expression, which is a marker of myofibroblasts, increased in the pcDNA3.0-GLIPR-2-transfected HK-2 cells. The cell migration assay demonstrated that the transfection of HK-2 with GLIPR-2 promoted cell migration following an EMT. Additionally, consistent with the effects of increased EGFR expression levels, we found that the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) was highly elevated in the pcDNA3.0-GLIPR-2-transfected group. Our study demonstrates that GLIPR-2 overexpression in HK-2 cells can potentiate EMT-like processes in this cell type through the ERK1/2 signaling pathway. GLIPR-2 may be responsible for the development of renal fibrosis by increasing the accumulation of interstitial fibroblasts.
authors.affiliation: Department of Clinical Laboratory, Xin Qiao Hospital, Third Military Medical University, Chong Qing, PR China.
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Huang
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Niu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Lele
authors.initials: L
authors.lastname: Zhang
authors.forename: Danni
authors.initials: D
authors.lastname: Ni
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pu
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D018450:Disease Progression; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*
chemical_list: C458481:GLIPR2 protein, human; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3