| 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
|
| リソース情報 |
| 遺伝子材料 |
AxCANCre (RDB01748)
AxCALNLNZ (RDB01750). |
