Melatonin inhibits human fibroblast-like synoviocyte proliferation via extracellular signal-regulated protein kinase/P21(CIP1)/P27(KIP1) pathways
DC Field | Value | Language |
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dc.contributor.author | Nah, Seong-Su | - |
dc.contributor.author | Won, Hye-Jin | - |
dc.contributor.author | Park, Hae Jeong | - |
dc.contributor.author | Ha, Eunyoung | - |
dc.contributor.author | Chung, Joo-Ho | - |
dc.contributor.author | Cho, Hong Yon | - |
dc.contributor.author | Baik, Hyung Hwan | - |
dc.date.accessioned | 2021-09-08T15:00:30Z | - |
dc.date.available | 2021-09-08T15:00:30Z | - |
dc.date.created | 2021-06-10 | - |
dc.date.issued | 2009-08 | - |
dc.identifier.issn | 0742-3098 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/119529 | - |
dc.description.abstract | The excessive proliferation and migration of synoviocytes are well-characterized phenomena that play key roles in the pathophysiology of rheumatoid arthritis (RA). Melatonin has been shown to have potent anti-proliferative effect in various cancer cells such as breast and prostate cancer cells. In this study, we examined the role of melatonin on synoviocyte proliferation in primary cultured human fibroblast-like synoviocytes (FLSs) by analyzing protein expression of P21(CIP1) (P21) and P27(KIP1) (P27), the cyclin-dependent kinase inhibitors that are important in cell cycle control, and the phosphorylation of mitogen-activated protein kinases (MAPKs). RA-FLS proliferation was determined by a [H-3]-thymidine incorporation assay. Western blot analysis was applied to examine the underlying mechanisms of melatonin's effect. Melatonin inhibited RA-FLS proliferation in a dose-dependent manner. It reduced proliferation of passage 2 FLSs by 25% at 10 mu m and by nearly 40% at 100 mu m concentrations. The inhibitory effect of melatonin on RA-FLS proliferation was also observed in passages 4 and 6. Melatonin upregulated the expression levels of P21 and P27 dose-dependently (24 hr), induced the phosphorylation of extracellular signal-regulated protein kinase (ERK) time-dependently (10 mu m), but did not affect phosphorylation of P38 in RA-FLSs. In addition, the expression of P21 and P27 triggered by melatonin was inhibited by the pretreatment of the ERK inhibitor, PD98059 (10 mu m). The anti-proliferative action of melatonin in RA-FLSs was also blocked by PD98059. Taken together, these results suggest that melatonin exerts the inhibitory effect of the proliferation of RA-FLSs through the activation of P21 and P27 mediated by ERK. Hence we suggest that melatonin could be used as a therapeutic agent for the treatment of RA. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.subject | ARTHRITIS SYNOVIAL FIBROBLASTS | - |
dc.subject | CELL-CYCLE ARREST | - |
dc.subject | RHEUMATOID-ARTHRITIS | - |
dc.subject | C-MYC | - |
dc.subject | JOINT DESTRUCTION | - |
dc.subject | INDUCE APOPTOSIS | - |
dc.subject | REACTIVE OXYGEN | - |
dc.subject | CDK-INHIBITORS | - |
dc.subject | CANCER CELLS | - |
dc.subject | EXPRESSION | - |
dc.title | Melatonin inhibits human fibroblast-like synoviocyte proliferation via extracellular signal-regulated protein kinase/P21(CIP1)/P27(KIP1) pathways | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Cho, Hong Yon | - |
dc.identifier.doi | 10.1111/j.1600-079X.2009.00689.x | - |
dc.identifier.scopusid | 2-s2.0-67649939037 | - |
dc.identifier.wosid | 000267706300008 | - |
dc.identifier.bibliographicCitation | JOURNAL OF PINEAL RESEARCH, v.47, no.1, pp.70 - 74 | - |
dc.relation.isPartOf | JOURNAL OF PINEAL RESEARCH | - |
dc.citation.title | JOURNAL OF PINEAL RESEARCH | - |
dc.citation.volume | 47 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 70 | - |
dc.citation.endPage | 74 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalResearchArea | Physiology | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.relation.journalWebOfScienceCategory | Physiology | - |
dc.subject.keywordPlus | ARTHRITIS SYNOVIAL FIBROBLASTS | - |
dc.subject.keywordPlus | CELL-CYCLE ARREST | - |
dc.subject.keywordPlus | RHEUMATOID-ARTHRITIS | - |
dc.subject.keywordPlus | C-MYC | - |
dc.subject.keywordPlus | JOINT DESTRUCTION | - |
dc.subject.keywordPlus | INDUCE APOPTOSIS | - |
dc.subject.keywordPlus | REACTIVE OXYGEN | - |
dc.subject.keywordPlus | CDK-INHIBITORS | - |
dc.subject.keywordPlus | CANCER CELLS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordAuthor | extracellular signal-regulated protein kinase | - |
dc.subject.keywordAuthor | fibroblast-like synoviocytes | - |
dc.subject.keywordAuthor | melatonin | - |
dc.subject.keywordAuthor | P21(CIP1) | - |
dc.subject.keywordAuthor | P27(KIP1) | - |
dc.subject.keywordAuthor | rheumatoid arthritis | - |
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