論文 - 詳細
| RRC ID | 58094 |
|---|---|
| 著者 | Niimi K, Adachi Y, Ishikawa H, Yamaguchi W, Kubota Y, Inagaki S, Furuyama T. |
| タイトル | Endothelial specific deletion of FOXO1 alters pericyte coverage in the developing retina. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Pericytes are mural cells that cover small blood vessels. While defects in pericyte coverage are known to be involved in various vessel related pathologies, including diabetic retinopathy, the molecular mechanisms underlying pericyte coverage are not fully understood. In this study, we investigated the contribution of the forkhead transcription factor FOXO1 in endothelial cells to pericyte coverage in the developing retina. We observed retinal pericytes in tamoxifen-inducible endothelium-specific Foxo1 deletion mice. Tamoxifen was injected at postnatal day 1-3 and the retinas were harvested at P21. Our results demonstrated that Foxo1 deletion in the endothelium affected arteriole pericyte morphology without altering pericyte number, proliferation, and apoptosis. We hypothesized that abnormal pericyte morphogenesis in the knockout retina was caused by impaired pericyte differentiation. FOXO1 silencing by siRNA in the primary artery endothelium further revealed that THBS1 (thrombospondin 1), which promotes pericyte differentiation via TGFβ activation, was reduced in the FOXO1-deficient endothelium. Immunohistochemistry of FOXO1 knockout mice showed reduced numbers of phospho-Smad3+ arteriole pericytes compared with wild-type mice. In addition, endothelium-pericyte co-culture analysis revealed that pericytes cultured with FOXO1-deficient endothelial cells failed to differentiate sufficiently; this failure was partially rescued by the addition of recombinant THBS1 to the supernatant. The findings suggest that endothelial FOXO1 contributes to pericyte differentiation via regulation of THBS1 expression. This study provides new insights into the molecular mechanism of pericyte coverage in the context of endothelium-derived regulation and highlights a new therapeutic target for pericyte-related pathology. |
| 巻・号 | 520(2) |
| ページ | 304-310 |
| 公開日 | 2019-12-3 |
| DOI | 10.1016/j.bbrc.2019.10.040 |
| PII | S0006-291X(19)31929-1 |
| PMID | 31601422 |
| MeSH | Animals Animals, Newborn Cell Differentiation Cells, Cultured Endothelial Cells Forkhead Box Protein O1 / genetics* Forkhead Box Protein O1 / metabolism Humans Mice, Inbred C57BL Mice, Knockout Pericytes / pathology* Retina / cytology* Retina / drug effects Retina / growth & development* Tamoxifen / pharmacology Thrombospondins / metabolism Transforming Growth Factor beta Umbilical Arteries / cytology |
| IF | 2.985 |
| 引用数 | 0 |
| 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 | 1 |
| 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 | |
| ヒト・動物細胞 | 10T1/2(RCB0247) |