論文 - 詳細
| RRC ID | 36049 |
|---|---|
| 著者 | Igarashi J, Okamoto R, Yamashita T, Hashimoto T, Karita S, Nakai K, Kubota Y, Takata M, Yamaguchi F, Tokuda M, Sakakibara N, Tsukamoto I, Konishi R, Hirano K. |
| タイトル | A key role of PGC-1α transcriptional coactivator in production of VEGF by a novel angiogenic agent COA-Cl in cultured human fibroblasts. |
| ジャーナル | Physiol Rep |
| Abstract |
We previously demonstrated a potent angiogenic effect of a newly developed adenosine-like agent namedCOA-Cl.COA-Cl exerted tube forming activity in human umbilical vein endothelial cells in the presence of normal human dermal fibroblasts (NHDF). We therefore explored whether and howCOA-Cl modulates gene expression and protein secretion ofVEGF, a master regulator of angiogenesis, inNHDFRT-PCRandELISArevealed thatCOA-Cl upregulatedVEGF mRNAexpression and protein secretion inNHDFHIF1α(hypoxia-inducible factor 1α), a transcription factor, andPGC-1α(peroxisome proliferator-activated receptor-γcoactivator-1α), a transcriptional coactivator, are known to positively regulate theVEGFgene. Immunoblot andRT-PCRanalyses revealed thatCOA-Cl markedly upregulated the expression ofPGC-1αprotein andmRNACOA-Cl had no effect on the expression ofHIF1αprotein andmRNAin both hypoxia and normoxia. SilencingPGC-1αgene, but notHIF1αgene, by small interferingRNAattenuated the ability ofCOA-Cl to promoteVEGFsecretion. When an N-terminal fragment ofPGC-1αwas cotransfected with its partner transcription factorERRα(estrogen-related receptor-α) inCOS-7 cells,COA-Cl upregulated the expression of the endogenousVEGF mRNA However,COA-Cl had no effect on the expression ofVEGF, whenHIF1αwas transfected.COA-Cl inducesVEGFgene expression and protein secretion in fibroblasts. The transcriptional coactivatorPGC-1α, in concert withERRα, plays a key role in theCOA-Cl-inducedVEGFproduction.COA-Cl-induced activation ofPGC-1α-ERRα-VEGFpathway has a potential as a novel means for therapeutic angiogenesis. |
| 巻・号 | 4(6) |
| 公開日 | 2016-3-1 |
| DOI | 10.14814/phy2.12742 |
| PII | 4/6/e12742 |
| PMID | 27033444 |
| PMC | PMC4814893 |
| MeSH | Adenosine / analogs & derivatives* Adenosine / pharmacology Angiogenesis Inducing Agents / pharmacology* Animals COS Cells Chlorocebus aethiops Dose-Response Relationship, Drug Fibroblasts / drug effects* Fibroblasts / metabolism Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha RNA Interference RNA, Messenger / metabolism Receptors, Estrogen / genetics Receptors, Estrogen / metabolism Signal Transduction / drug effects Time Factors Transcription Factors / genetics Transcription Factors / metabolism* Transcription, Genetic Transcriptional Activation Transfection Up-Regulation Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / metabolism* |
| 引用数 | 6 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCMFlag_hsESRRA (RDB06260) |