First Author | Heuchel R | Year | 1999 |
Journal | Proc Natl Acad Sci U S A | Volume | 96 |
Issue | 20 | Pages | 11410-5 |
PubMed ID | 10500190 | Mgi Jnum | J:69710 |
Mgi Id | MGI:2135339 | Doi | 10.1073/pnas.96.20.11410 |
Citation | Heuchel R, et al. (1999) Platelet-derived growth factor beta receptor regulates interstitial fluid homeostasis through phosphatidylinositol-3' kinase signaling. Proc Natl Acad Sci U S A 96(20):11410-5 |
abstractText | Platelet-derived growth factor (PDGF) isoforms lead to mitogenic, survival, and chemotactic responses in a variety of mesenchymal cell types during development and in the adult. We have studied the importance of phosphatidylinositol-3' kinase (PI3K) signaling in these responses by mutating the PI3K-binding sites in the PDGF-beta receptor by gene targeting in embryonic stem cells. Homozygous mutant mice developed normally; however, cells derived from the mutants were less chemotactic and had largely lost their ability to contract collagen gels in response to PDGF. Injection of a mast cell degranulating agent in mice led to a decrease in interstitial fluid pressure resulting in edema formation. In contrast to wild-type mice, mutant mice were unable to normalize the pressure after treatment with PDGF. Taken together, these observations suggest a function for PDGF signaling through PI3K in interstitial fluid homeostasis by modulating the tension between cells and extracellular matrix structures. |