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Platelet-derived growth factor beta receptor regulates interstitial fluid homeostasis through phosphatidylinositol-3' kinase signaling
Ludwiginstitutet för Cancerforskning.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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1999 (English)In: Proc Natl Acad Sci U S A, Vol. 96, no 20, 11410-5 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
1999. Vol. 96, no 20, 11410-5 p.
URN: urn:nbn:se:uu:diva-52742PubMedID: 10500190OAI: oai:DiVA.org:uu-52742DiVA: diva2:80652
Available from: 2007-03-13 Created: 2007-03-13 Last updated: 2011-01-14

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Heuchel, RainerReed, Rolf KRubin, KristoferClaesson-Welsh, LenaHeldin, Carl-Henrik
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