In vivo silencing of amphiregulin by a novel effective Self-Assembled-Micelle inhibitory RNA ameliorates renal fibrosis via inhibition of EGFR signals
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Son, Seung Seob | - |
dc.contributor.author | Hwang, Soohyun | - |
dc.contributor.author | Park, Jun Hong | - |
dc.contributor.author | Ko, Youngho | - |
dc.contributor.author | Yun, Sung-Il | - |
dc.contributor.author | Lee, Ji-Hye | - |
dc.contributor.author | Son, Beomseok | - |
dc.contributor.author | Kim, Tae Rim | - |
dc.contributor.author | Park, Han-Oh | - |
dc.contributor.author | Lee, Eun Young | - |
dc.date.accessioned | 2021-08-11T08:26:44Z | - |
dc.date.available | 2021-08-11T08:26:44Z | - |
dc.date.issued | 2021-01-26 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/1934 | - |
dc.description.abstract | Amphiregulin (AREG) is a transmembrane glycoprotein recently implicated in kidney fibrosis. Previously, we reported that the AREG-targeting Self-Assembled-Micelle inhibitory RNA (SAMiRNA-AREG) alleviated fibrosis by stably silencing the AREG gene, and reduced the side effects of conventional siRNA treatment of pulmonary fibrosis. However, the therapeutic effect of SAMiRNA-AREG in renal fibrosis has not been studied until now. We used two animal models of renal fibrosis generated by a unilateral ureteral obstruction (UUO) and an adenine diet (AD) to investigate whether SAMiRNA-AREG inhibited renal fibrosis. To investigate the delivery of SAMiRNA-AREG to the kidney, Cy5-labeled SAMiRNA-AREG was injected into UUO- and AD-induced renal fibrosis models. In both kidney disease models, SAMiRNA-AREG was delivered primarily to the damaged kidney. We also confirmed the protective effect of SAMiRNA-AREG in renal fibrosis models. SAMiRNA-AREG markedly decreased the UUO- and AD-induced AREG mRNA expression. Furthermore, the mRNA expression of fibrosis markers, including alpha -smooth muscle actin, fibronectin, alpha 1(I) collagen, and alpha 1(III) collagen in the UUO and AD-induced kidneys, was diminished in the SAMiRNA-AREG-treated mice. The transcription of inflammatory markers (tumor necrosis factor-alpha and monocyte chemoattractant protein-1) and adhesion markers (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) was attenuated. The hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining results showed that SAMiRNA-AREG decreased renal fibrosis, AREG expression, and epidermal growth factor receptor (EGFR) phosphorylation in the UUO- and AD-induced models. Moreover, we studied the effects of SAMiRNA-AREG in response to TGF-beta 1 in mouse and human proximal tubule cells, and mouse fibroblasts. TGF-beta 1-induced extracellular matrix production and myofibroblast differentiation were attenuated by SAMiRNA-AREG. Finally, we confirmed that upregulated AREG in the UUO or AD models was mainly localized in the distal tubules. In conclusion, SAMiRNA-AREG represents a novel siRNA therapeutic for renal fibrosis by suppressing EGFR signals. | - |
dc.publisher | Nature Publishing Group | - |
dc.title | In vivo silencing of amphiregulin by a novel effective Self-Assembled-Micelle inhibitory RNA ameliorates renal fibrosis via inhibition of EGFR signals | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/s41598-021-81726-2 | - |
dc.identifier.scopusid | 2-s2.0-85099874733 | - |
dc.identifier.wosid | 000667505700013 | - |
dc.identifier.bibliographicCitation | Scientific Reports, v.11, no.1 | - |
dc.citation.title | Scientific Reports | - |
dc.citation.volume | 11 | - |
dc.citation.number | 1 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | FACTOR RECEPTOR-LIGAND | - |
dc.subject.keywordPlus | URETERAL OBSTRUCTION | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | TISSUE | - |
dc.subject.keywordPlus | MYOFIBROBLASTS | - |
dc.subject.keywordPlus | NANOPARTICLES | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | NEPHROPATHY | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordAuthor | 의약학 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(31538) 22, Soonchunhyang-ro, Asan-si, Chungcheongnam-do, Republic of Korea+82-41-530-1114
COPYRIGHT 2021 by SOONCHUNHYANG UNIVERSITY ALL RIGHTS RESERVED.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.