Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 심소연 | * |
dc.date.accessioned | 2022-03-29T16:31:00Z | - |
dc.date.available | 2022-03-29T16:31:00Z | - |
dc.date.issued | 2022 | * |
dc.identifier.issn | 2093-596X | * |
dc.identifier.other | OAK-31134 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/260928 | - |
dc.description.abstract | Background: Diabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-β (TGF-β) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-β type 1 receptor kinase (ALK5), in retarding the progression of DN, both in vivo, using a diabetic mouse model (db/db mice), and in vitro, in podocytes and mesangial cells. Methods: In vivo study: 8-week-old db/db mice were orally administered EW-7197 at a dose of 5 or 20 mg/kg/day for 10 weeks. Metabolic parameters and renal function were monitored. Glomerular histomorphology and renal protein expression were evaluated by histochemical staining and Western blot analyses, respectively. In vitro study: DN was induced by high glucose (30 mM) in podocytes and TGF-β (2 ng/mL) in mesangial cells. Cells were treated with EW-7197 (500 nM) for 24 hours and the mechanism associated with the attenuation of DN was investigated. Results: Enhanced albuminuria and glomerular morphohistological changes were observed in db/db compared to that of the nondiabetic (db/m) mice. These alterations were associated with the activation of the TGF-β signaling pathway. Treatment with EW-7197 significantly inhibited TGF-β signaling, inflammation, apoptosis, reactive oxygen species, and endoplasmic reticulum stress in diabetic mice and renal cells. Conclusion: EW-7197 exhibits renoprotective effect in DN. EW-7197 alleviates renal fibrosis and inflammation in diabetes by inhibiting downstream TGF-β signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN. Copyright © 2022 Korean Endocrine Society. | * |
dc.language | English | * |
dc.publisher | Korean Endocrine Society | * |
dc.subject | Activin receptor-like kinase 5 | * |
dc.subject | Diabetic nephropathies | * |
dc.subject | Glomerular mesangial cells | * |
dc.subject | Podocytes | * |
dc.subject | Transforming growth factor beta | * |
dc.title | EW-7197 Attenuates the Progression of Diabetic Nephropathy in db/db Mice through Suppression of Fibrogenesis and Inflammation | * |
dc.type | Article | * |
dc.relation.issue | 1 | * |
dc.relation.volume | 37 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.index | KCI | * |
dc.relation.startpage | 96 | * |
dc.relation.lastpage | 111 | * |
dc.relation.journaltitle | Endocrinology and Metabolism | * |
dc.identifier.doi | 10.3803/ENM.2021.1305 | * |
dc.identifier.wosid | WOS:000764890400010 | * |
dc.identifier.scopusid | 2-s2.0-85126662204 | * |
dc.author.google | Ha K.B. | * |
dc.author.google | Sangartit W. | * |
dc.author.google | Jeong A.R. | * |
dc.author.google | Lee E.S. | * |
dc.author.google | Kim H.M. | * |
dc.author.google | Shim S. | * |
dc.author.google | Kukongviriyapan U. | * |
dc.author.google | Kim D.-K. | * |
dc.author.google | Lee E.Y. | * |
dc.author.google | Chung C.H. | * |
dc.contributor.scopusid | 심소연(16686809100;58221146900) | * |
dc.date.modifydate | 20240315122616 | * |