Gemigliptin Inhibits Interleukin-1β–Induced Endothelial Mesenchymal Transition via Canonical-Bone Morphogenetic Protein Pathway
DC Field | Value | Language |
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dc.contributor.author | Hong, Oak-Kee | - |
dc.contributor.author | Lee, Seong-Su | - |
dc.contributor.author | Yoo, Soon Jib | - |
dc.contributor.author | Lee, Min-Kyung | - |
dc.contributor.author | Kim, Mee-Kyoung | - |
dc.contributor.author | Baek, Ki-Hyun | - |
dc.contributor.author | Song, Ki-Ho | - |
dc.contributor.author | Kwon, Hyuk-Sang | - |
dc.date.accessioned | 2022-07-08T00:23:37Z | - |
dc.date.available | 2022-07-08T00:23:37Z | - |
dc.date.created | 2021-05-13 | - |
dc.date.issued | 2020-06 | - |
dc.identifier.issn | 2093-596X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/145549 | - |
dc.description.abstract | Background: Endothelial-to-mesenchymal transition (EndMT) contributes to inflammatory conditions inducing conversion of endothelial cells (ECs) into activated fibroblasts, promoting fibrotic diseases. Pm-inflammatory cytokine is the most potent inducer of EndMT. We investigated inhibition of interleukin-1 beta (IL-1 beta)-induced EndMT by gemigliptin, a dipeptidyl peptidase-IV inhibitor. Methods: We exposed human umbilical vein endothelial cells (HUVECs) to 10 ng/mL IL-1 beta/20 mu M gemigliptin and analyzed the expression of endothelial, smooth muscle, mesenchymal, and osteoblastic markets, bone motphogenetic protein (BMP), Smad, and non-Smad signaling pathway proteins. Results: Morphological changes showed gemigliptin blocked IL-1 beta-induced EndMT. upregulated EC madcers, and downregulated smooth muscle and mesenchymal markers. IL-1 beta activation of HUVECs is initiated by the BMP/Smad and non-smad BMP signaling pathways. Gemigliptin inhibited IL-1 beta induction of BMP2 and 7, activin receptor type IA, BMP receptor type IA, and BMP receptor type II. Reversal of IL-1 beta-mediated inhibition of BMP-induced Smad1/5/8, Smad2, and Smad3 phosphorylation by gemigliptin suggests involvement of the Smad pathway in gemigliptin action. In the non-Smad BMP pathway, gemigliptin treatment significantly increased the deactivation of extracellular regulated protein kinase (ERK), p38, and JNK by IL-1 beta. Gemigliptin treatment suppressed BMP-2-induced expression of key osteoblastic markers including osterix, runt-related transcription factor 2, and hepcidin during IL-1 beta-induced EndMT. Conclusion: We demonstrated a novel protective mechanism of gemigliptin against fibrosis by suppressing IL-1 beta-induced EndMT. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | KOREAN ENDOCRINE SOC | - |
dc.title | Gemigliptin Inhibits Interleukin-1β–Induced Endothelial Mesenchymal Transition via Canonical-Bone Morphogenetic Protein Pathway | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Min-Kyung | - |
dc.identifier.doi | 10.3803/EnM.2020.35.2.384 | - |
dc.identifier.scopusid | 2-s2.0-85089364108 | - |
dc.identifier.wosid | 000596724000020 | - |
dc.identifier.bibliographicCitation | ENDOCRINOLOGY AND METABOLISM, v.35, no.2, pp.384 - 395 | - |
dc.relation.isPartOf | ENDOCRINOLOGY AND METABOLISM | - |
dc.citation.title | ENDOCRINOLOGY AND METABOLISM | - |
dc.citation.volume | 35 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 384 | - |
dc.citation.endPage | 395 | - |
dc.type.rims | ART | - |
dc.identifier.kciid | ART002602450 | - |
dc.description.journalClass | 1 | - |
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 | DIPEPTIDYL PEPTIDASE-4 INHIBITION | - |
dc.subject.keywordPlus | LINAGLIPTIN | - |
dc.subject.keywordPlus | IL-1-BETA | - |
dc.subject.keywordPlus | FIBROSIS | - |
dc.subject.keywordPlus | INDUCE | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordAuthor | LC15-0444 | - |
dc.subject.keywordAuthor | Dipeptidyl-peptidase IV inhibitors | - |
dc.subject.keywordAuthor | Interleukin-1beta | - |
dc.subject.keywordAuthor | Bone morphogenetic proteins | - |
dc.subject.keywordAuthor | Endothelial-to-mesenchymal transition | - |
dc.identifier.url | https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2020.35.2.384 | - |
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