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enrichment analyses (Figure 2C). Interestingly, genes implicated in PDGF binding (Pdgfa, Pdgfb, Pdap1, Pdgfra, Pdgfrb, Col1a1, Col1a2, Col2a1, Col3a1, Col4a1, Col5a1 and Col6a1) were most over-represented within the up-regu- lated genes, followed by ECM structural constituents and genes referring to collagen binding.
Expression dynamics of platelet-derived growth factor signaling components during the development of myelofibrosis
Platelet-derived growth factors and their receptors are linked to bone marrow fibrosis, as was inferred from their increased expression in PMF patients.9,10 However, data addressing the expression dynamics during the develop-
ment of myelofibrosis are sparse. In order to characterize the expression pattern of PDGF signaling components at different stages of bone marrow fibrosis, we analyzed gene expression of the ligand and receptor genes in the bone marrow of Gata-1low mice by quantitative PCR (qPCR). Here, we observed that gene expression of both receptor genes Pdgfra and Pdgfrb was highly induced in early fibrotic bone marrow from 10-month-old Gata-1low mice and remained increased in overt fibrotic bone mar- row of 15-month-old Gata-1low mice (Figure 3A and B). Interestingly, Pdgfrb gene expression was significantly decreased in pre-fibrotic bone marrow of 5-month-old Gata-1low mice, as also detected for Col1a1 gene expres- sion. qPCR analyses of the ligand genes Pdgfa and Pdgfb
B
C
A
Figure 2. RNA sequencing analyses showing gene expression of receptor tyrosine kinases (RTK), their ligands and gene ontology enrichment analy- sis. Total RNA from femoral bone mar- row of 10-month-old mice (n=3 Gata-1low vs. n=3 wild-type mice) was analyzed. (A) Gene expression of RTK. (B) Gene expression of their cognate ligands. (C) Gene ontology enrichment analysis of over-expressed genes.
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haematologica | 2020; 105(8)