EW-7197 Attenuates the Progression of Diabetic Nephropathy in db/db Mice through Suppression of Fibrogenesis and Inflammation
DC Field | Value | Language |
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dc.contributor.author | Ha, Kyung Bong | - |
dc.contributor.author | Sangartit, Weerapon | - |
dc.contributor.author | Jeong, Ah Reum | - |
dc.contributor.author | Lee, Eun Soo | - |
dc.contributor.author | Kim, Hong Min | - |
dc.contributor.author | Shim, Soyeon | - |
dc.contributor.author | Kukongyiriyapan, Upa | - |
dc.contributor.author | Kim, Dae-Kee | - |
dc.contributor.author | Lee, Eun Young | - |
dc.contributor.author | Chung, Choon Hee | - |
dc.date.accessioned | 2022-03-24T05:40:03Z | - |
dc.date.available | 2022-03-24T05:40:03Z | - |
dc.date.issued | 2022-02-01 | - |
dc.identifier.issn | 2093-596X | - |
dc.identifier.issn | 2093-5978 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/20547 | - |
dc.description.abstract | Background: Diabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-f3 (TGF-f3) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-f3 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-f3 (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-f3 signaling pathway. Treatment with EW-7197 significantly inhibited TGF-f3 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-f3 signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN. | - |
dc.format.extent | 16 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | 대한내분비학회 | - |
dc.title | EW-7197 Attenuates the Progression of Diabetic Nephropathy in db/db Mice through Suppression of Fibrogenesis and Inflammation | - |
dc.type | Article | - |
dc.publisher.location | 대한민국 | - |
dc.identifier.doi | 10.3803/EnM.2021.1305 | - |
dc.identifier.scopusid | 2-s2.0-85126662204 | - |
dc.identifier.wosid | 000764890400010 | - |
dc.identifier.bibliographicCitation | Endocrinology and Metabolism, v.37, no.1, pp 96 - 111 | - |
dc.citation.title | Endocrinology and Metabolism | - |
dc.citation.volume | 37 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 96 | - |
dc.citation.endPage | 111 | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART002814918 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | PROTEIN-KINASE-C | - |
dc.subject.keywordPlus | ENDOPLASMIC-RETICULUM STRESS | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | FIBROSIS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | INHIBITOR | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | PODOCYTES | - |
dc.subject.keywordAuthor | Diabetic nephropathies | - |
dc.subject.keywordAuthor | Glomerular mesangial cells | - |
dc.subject.keywordAuthor | Podocytes | - |
dc.subject.keywordAuthor | Transforming growth factor beta | - |
dc.subject.keywordAuthor | Activin receptor-like kinase 5 | - |
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