Cited 9 times in
Microparticles derived from human erythropoietin mRNA-transfected mesenchymal stem cells inhibit epithelial-to-mesenchymal transition and ameliorate renal interstitial fibrosis
DC Field | Value | Language |
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dc.contributor.author | 김석형 | - |
dc.contributor.author | 박형천 | - |
dc.contributor.author | 지종현 | - |
dc.contributor.author | 최훈영 | - |
dc.date.accessioned | 2020-12-01T17:03:13Z | - |
dc.date.available | 2020-12-01T17:03:13Z | - |
dc.date.issued | 2020-09 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/180101 | - |
dc.description.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 Madin-Darby 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 co-treatment 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. Results: TGF-β1 treatment significantly increased α-SMA and fibronectin expression in MDCK cells and decreased that of E-cadherin, while co-treatment with rhEPO, MOCK-MPs, or hEPO-MPs markedly attenuated these changes. In addition, rhEPO and hEPO-MP treatment effectively decreased phosphorylated Smad2 and Smad3, as well as phosphorylated p38 mitogen-activated protein kinase (MAPK) expression, suggesting that rhEPO and rhEPO-MPs can inhibit TGF-β1-induced EMT via both Smad and non-Smad pathways. rhEPO and hEPO-MP treatment also significantly attenuated the extent of renal TIF after 1 week of UUO compared to MOCK-MPs, with hEPO-MPs significantly reducing myofibroblast and F4/80+ macrophage infiltration as well as EMT marker expression in UUO renal tissues in a similar manner to rhEPO. Conclusions: Our results demonstrate that hEPO-MPs modulate TGF-β1-induced EMT in MDCK cells via the Smad2, Smad3, and p38 MAPK pathways and significantly attenuated renal TIF in UUO kidneys. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | BioMed Central | - |
dc.relation.isPartOf | STEM CELL RESEARCH & THERAPY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Microparticles derived from human erythropoietin mRNA-transfected mesenchymal stem cells inhibit epithelial-to-mesenchymal transition and ameliorate renal interstitial fibrosis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Mirae Lee | - |
dc.contributor.googleauthor | Seok-Hyung Kim | - |
dc.contributor.googleauthor | Jong Hyun Jhee | - |
dc.contributor.googleauthor | Tae Yeon Kim | - |
dc.contributor.googleauthor | Hoon Young Choi | - |
dc.contributor.googleauthor | Hyung Jong Kim | - |
dc.contributor.googleauthor | Hyeong Cheon Park | - |
dc.identifier.doi | 10.1186/s13287-020-01932-z | - |
dc.contributor.localId | A04526 | - |
dc.contributor.localId | A01759 | - |
dc.contributor.localId | A03970 | - |
dc.contributor.localId | A04226 | - |
dc.relation.journalcode | J02681 | - |
dc.identifier.eissn | 1757-6512 | - |
dc.identifier.pmid | 32993806 | - |
dc.subject.keyword | Epithelial-to-mesenchymal transition | - |
dc.subject.keyword | Erythropoietin | - |
dc.subject.keyword | Microparticles | - |
dc.subject.keyword | Renal fibrosis | - |
dc.subject.keyword | Transforming growth factor-β1 | - |
dc.contributor.alternativeName | Kim, Seok Hyung | - |
dc.contributor.affiliatedAuthor | 김석형 | - |
dc.contributor.affiliatedAuthor | 박형천 | - |
dc.contributor.affiliatedAuthor | 지종현 | - |
dc.contributor.affiliatedAuthor | 최훈영 | - |
dc.citation.volume | 11 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 422 | - |
dc.identifier.bibliographicCitation | STEM CELL RESEARCH & THERAPY, Vol.11(1) : 422, 2020-09 | - |
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