論文 - 詳細
| RRC ID | 1613 |
|---|---|
| 著者 | Gao Z, Sasaoka T, Fujimori T, Oya T, Ishii Y, Sabit H, Kawaguchi M, Kurotaki Y, Naito M, Wada T, Ishizawa S, Kobayashi M, Nabeshima Y, Sasahara M. |
| タイトル | Deletion of the PDGFR-beta gene affects key fibroblast functions important for wound healing. |
| ジャーナル | J Biol Chem |
| Abstract |
This study provides new perspectives of the unique aspects of platelet-derived growth factor beta-receptor (PDGFR-beta) signaling and biological responses through the establishment of a mutant mouse strain in which two loxP sequences were inserted into the introns of PDGFR-beta genome sequences. Isolation of skin fibroblasts from the mutant mice and Cre recombinase transfection in vitro induced PDGFR-beta gene deletion (PDGFR-betaDelta/Delta). The resultant depletion of the PDGFR-beta protein significantly attenuated platelet-derived growth factor (PDGF)-BB-induced cell migration, proliferation, and protection from H2O2-induced apoptosis of the cultured PDGFR-betaDelta/Delta dermal fibroblasts. PDGF-AA and fetal bovine serum were mitogenic and anti-apoptotic but were unable to induce the migration in PDGFR-beta Delta/Delta fibroblasts. Concerning the PDGF signaling, PDGF-BB-induced phosphorylation of Akt, ERK1/2, and JNK, but not p38, decreased in PDGFR-betaDelta/Delta fibroblasts, but PDGF-AA-induced signaling was not altered. Overexpression of the phospholipid phosphatases, SHIP2 and/or PTEN, inhibited PDGF-BB-induced phosphorylation of Akt and ERK1/2 in PDGFR-betaDelta/Delta fibroblasts but did not affect that of JNK and p38. These results indicate that disruption of distinct PDGFR-beta signaling pathways in PDGFR-betaDelta/Delta dermal fibroblasts impaired their proliferation and survival, but completely inhibits migratory response, and that PDGF-BB-induced phosphorylation of Akt and ERK1/2 possibly mediated by PDGFR-alpha is regulated, at least in part, by the lipid phosphatases SHIP2 and/or PTEN. Thus, the PDGFR-beta function on dermal fibroblasts appears to be critical in PDGF-BB action for skin wound healing and is clearly distinctive from that of PDGFR-alpha in the ligand-induced biological responses and the underlying properties of cellular signaling. |
| 巻・号 | 280(10) |
| ページ | 9375-89 |
| 公開日 | 2005-3-11 |
| DOI | 10.1074/jbc.M413081200 |
| PII | S0021-9258(19)62955-8 |
| PMID | 15590688 |
| MeSH | Animals DNA Primers Fibroblasts / physiology* Gene Deletion* Genotype Humans Integrases / metabolism Mice Mice, Knockout Receptor, Platelet-Derived Growth Factor beta / deficiency Receptor, Platelet-Derived Growth Factor beta / genetics* Recombinant Proteins / metabolism Restriction Mapping Skin Transfection Wound Healing / physiology* Wounds and Injuries / genetics Wounds and Injuries / pathology* |
| IF | 4.238 |
| 引用数 | 75 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 遺伝子材料 | AxCANCre (RDB01748) AxCALNLNZ (RDB01750). |