PDGFRA and Associated Diseases
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Overview of PDGFRA
In humans, platelet-derived growth factor receptor A (PDGFRA, also known as PDGFRα or cluster of differentiation 140a, CD140a) is a protein encoded by the PDGFRA gene. PDGFRA can be found on the surface of numerous different types of cells. When PDGFRA binds to the specific isoforms of platelet-derived growth factors, it becomes active in different cell signaling pathways that cause responses including cell proliferation and differentiation. PDGFRA is essential for the development of specific tissues and organs during embryogenesis and for maintaining certain tissues and organs throughout life, especially hematologic tissues.
PDGFRA in Disease
PDGFRA takes part in the progression of diseases such as human cytomegalovirus-related disease and also participates in a lot of cancers like papillary thyroid cancer.
- Human cytomegalovirus-related disease
The activation of PDGFRA is associated with human cytomegalovirus (HCMV) infection, which leads to HCMV-related disease. HCMV, a common human herpesvirus, can harm an immunocompromised host and is life-threatening to the unborn child. In various human cell types, both HCMV isolated from the laboratory and clinic can phosphorylate the tyrosine of PDGFRA by HCMV glycoprotein B. When cells are treated with glycoprotein B-neutralizing antibodies, the phosphorylation of PDGFRA is inhibited. The cells are non-permissive to HCMV entry, viral gene expression, and production of infectious progeny when PDGFRA is deleted or functionally blocked, which can be restored with the re-introduction of the human PDGFRA gene. Taken together, PDGFRA is a novel target for anti-HCMV therapies.
- Papillary thyroid cancer
PDGFRA is related to the treatment resistance and disease recurrence of papillary thyroid carcinoma (PTC). Patients with aggressive PTC variations frequently need recurrent operations or higher radioactive iodine doses to treat metastatic illness. PDGFRA specifically disrupts the transcriptional activity of TTF1 resulting in the dedifferentiation of PTC and the destruction of thyroglobulin production and sodium iodide transport, which are considered to the poor outcomes in PTC patients. Along with encouraging a more invasive and migrating cell phenotype, PDGFR also significantly increases the development of xenograft tumors. Resistance to radioactive iodine therapy is predicted by low nuclear TTF1 levels and high PDGFR levels. Thus, blocking PDGFRA signaling can be an attractive strategy for PTC treatment.
Fig.1 Low PDGFRA and high TTF1 predict better progression-free survival curve. (Lopez-Campistrous, 2016)
Creative Biolabs has expertise in the process of developing gene treatments. You can considerably speed up your clinical study by collaborating with us. Our objective is to provide a wide range of services, including gene therapy, for your projects. Please feel free to contact us for more details about your PDGFRA project.
References
- Soroceanu, L.; et al. Platelet-derived growth factor-α receptor activation is required for human cytomegalovirus infection. Nature. 2008, 455: 391–395 (2008).
- Lopez-Campistrous, A.; et al. PDGFRα Regulates Follicular Cell Differentiation Driving Treatment Resistance and Disease Recurrence in Papillary Thyroid Cancer. EBioMedicine. 2016, 12: 86–97.
