Microparticles derived from human erythropoietin mRNA-transfected mesenchymal stem cells inhibit epithelial-to-mesenchym
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RESEARCH
Open Access
Microparticles derived from human erythropoietin mRNA-transfected mesenchymal stem cells inhibit epithelialto-mesenchymal transition and ameliorate renal interstitial fibrosis Mirae Lee1,2, Seok-hyung Kim2,3, Jong Hyun Jhee2, Tae Yeon Kim2, Hoon Young Choi2,4, Hyung Jong Kim5 and Hyeong Cheon Park1,2,4*
Abstract Background: Renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of chronic kidney disease (CKD) and its pathogenesis involves epithelial-to-mesenchymal transition (EMT) upon renal injury. Recombinant human erythropoietin (rhEPO) has been shown to display novel cytoprotective effects, in part by inhibiting transforming growth factor (TGF)-β1-induced EMT. Here, we evaluated the inhibitory effects of microparticles (MPs) derived from human EPO gene-transfected kidney mesenchymal stem cells (hEPO-KMSCs) against TGF-β1-induced EMT in MadinDarby canine kidney (MDCK) cells and against TIF in mouse kidneys with unilateral ureteral obstruction (UUO). Methods: EMT was induced in MDCK cells by treatment with TGF-β1 (5 ng/mL) for 48 h and then inhibited by cotreatment with rhEPO (100 IU/mL), mock gene-transfected KMSC-derived MPs (MOCK-MPs), or hEPO-KMSC-derived MPs (hEPO-MPs) for a further 48 h. UUO was induced in FVB/N mice, which were then treated with rhEPO (1000 IU/kg, intraperitoneally, every other day for 1 week), MOCK-MPs, or hEPO-MPs (80 μg, intravenously). Alpha-smooth muscle actin (α-SMA), fibronectin, and E-cadherin expression were evaluated in MDCK cells and kidney tissues, and the extent of TIF in UUO kidneys was assessed by immunohistochemical staining. (Continued on next page)
* Correspondence: [email protected] 1 Graduate Program of Nano Science and Technology, Yonsei University, Seoul, Korea 2 Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Full list of author information is available at the end of the article
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