Sökning: onr:"swepub:oai:DiVA.org:uu-400900" >
Platelet-derived gr...
Platelet-derived growth factor receptor β activation and regulation in murine myelofibrosis
-
Kramer, Frederike (författare)
-
Dernedde, Jens (författare)
-
- Mezheyeuski, Artur (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
-
visa fler...
-
Tauber, Rudolf (författare)
-
- Micke, Patrick (författare)
- Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
-
Kappert, Kai (författare)
-
visa färre...
-
(creator_code:org_t)
- 2019-10-31
- 2020
- Engelska.
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 105:8, s. 2083-2094
- Relaterad länk:
-
https://doi.org/10.3...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://haematologic...
-
https://urn.kb.se/re...
-
https://doi.org/10.3...
-
visa färre...
Abstract
Ämnesord
Stäng
- There is prevailing evidence to suggest a decisive role for platelet-derived growth factors (PDGF) and their receptors in primary myelofibrosis. While PDGF receptor β (PDGFRβ) expression is increased in bone marrow stromal cells of patients correlating with the grade of myelofibrosis, knowledge on the precise role of PDGFRβ signaling in myelofibrosis is sparse. Using the Gata-1low mouse model for myelofibrosis, we applied RNA sequencing, protein expression analyses, multispectral imaging and, as a novel approach in bone marrow tissue, an in situ proximity ligation assay to provide a detailed characterization of PDGFRβ signaling and regulation during development of myelofibrosis. We observed an increase in PDGFRβ and PDGF-B protein expression in overt fibrotic bone marrow, along with an increase in PDGFRβ–PDGF-B interaction, analyzed by proximity ligation assay. However, PDGFRβ tyrosine phosphorylation levels were not increased. We therefore focused on regulation of PDGFRβ by protein tyrosine phosphatases as endogenous PDGFRβ antagonists. Gene expression analyses showed distinct expression dynamics among PDGFRβ-targeting phosphatases. In particular, we observed enhanced T-cell protein tyrosine phosphatase protein expression and PDGFRβ–T-cell protein tyrosine phosphatase interaction in early and overt fibrotic bone marrow of Gata-1low mice. In vitro, T-cell protein tyrosine phosphatase (Ptpn2) knockdown increased PDGFRβ phosphorylation at Y751 and Y1021, leading to enhanced downstream signaling in fibroblasts. Furthermore, Ptpn2 knockdown cells showed increased growth rates when exposed to low-serum growth medium. Taken together, PDGF signaling is differentially regulated during myelofibrosis. Protein tyrosine phosphatases, which have so far not been examined during disease progression, are novel and hitherto unrecognized components in myelofibrosis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Nyckelord
- Chronic Myeloproliferative Disorders
- Platelet-derived growth factors
- Protein tyrosine phosphatases
- Protein-protein interaction
- Proximity ligation assay
- Patologi
- Pathology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas