scholarly journals Cryo-Electron Microscopy Structure and Interactions of the Human Cytomegalovirus gHgLgO Trimer with Platelet-Derived Growth Factor Receptor Alpha

mBio ◽  
2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Jing Liu ◽  
Adam Vanarsdall ◽  
Dong-Hua Chen ◽  
Andrea Chin ◽  
David Johnson ◽  
...  
Keyword(s):  
Birth Defects ◽  
Adult Population ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
The Body ◽  
Platelet Derived Growth Factor ◽  
Cryo Electron Microscopy ◽  
Factor Receptor Alpha ◽  
Complex Protein ◽  
Different Cell Types

HCMV is a herpesvirus that infects a large percentage of the adult population and causes significant levels of disease in immunocompromised individuals and birth defects in the developing fetus. The virus encodes a complex protein machinery that coordinates infection of different cell types in the body, including a trimer formed of gH, gL, and gO subunits.

scholarly journals Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenichi Kimura ◽  
Karina Ramirez ◽  
Tram Anh Vu Nguyen ◽  
Yoshito Yamashiro ◽  
Aiko Sada ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Pressure Overload ◽  
Vascular Diseases ◽  
Cell Types ◽  
Lineage Tracing ◽  
Neointima Formation ◽  
Artery Ligation ◽  
Carotid Artery Ligation ◽  
Factor Receptor Alpha ◽  
Adventitial Cells

AbstractThe maladaptive remodeling of vessel walls with neointima formation is a common feature of proliferative vascular diseases. It has been proposed that neointima formation is caused by the dedifferentiation of mature smooth muscle cells (SMCs). Recent evidence suggests that adventitial cells also participate in neointima formation; however, their cellular dynamics are not fully understood. In this study, we utilized a lineage tracing model of platelet-derived growth factor receptor alpha (PDGFRa) cells and examined cellular behavior during homeostasis and injury response. PDGFRa marked adventitial cells that were largely positive for Sca1 and a portion of medial SMCs, and both cell types were maintained for 2 years. Upon carotid artery ligation, PDGFRa-positive (+) cells were slowly recruited to the neointima and exhibited an immature SMC phenotype. In contrast, in a more severe wire denudation injury, PDGFRa+ cells were recruited to the neointima within 14 days and fully differentiated into SMCs. Under pressure overload induced by transverse aortic constriction, PDGFRa+ cells developed marked adventitial fibrosis. Taken together, our observations suggest that PDGFRa+ cells serve as a reservoir of adventitial cells and a subset of medial SMCs and underscore their context-dependent response to vascular injuries.

scholarly journals Sorafenib is a potent inhibitor of FIP1L1-PDGFRα and the imatinib-resistant FIP1L1-PDGFRα T674I mutant

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1374-1376 ◽  
Author(s):  
Els Lierman ◽  
Cedric Folens ◽  
Elizabeth H. Stover ◽  
Nicole Mentens ◽  
Helen Van Miegroet ◽  
...  
Keyword(s):  
Low Dose ◽  
Potent Inhibitor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Low Doses ◽  
Chronic Eosinophilic Leukemia ◽  
Nanomolar Concentration ◽  
Imatinib Resistant ◽  
Factor Receptor Alpha ◽  
Induced Apoptosis

Abstract The FIP1L1-PDGFRA oncogene is a common cause of chronic eosinophilic leukemia (CEL), and encodes an activated tyrosine kinase that is inhibited by imatinib. FIP1L1-PDGFRA–positive patients with CEL respond to low-dose imatinib therapy, but resistance due to acquired T674I mutation has been observed. We report here the identification of sorafenib as a potent inhibitor of the FIP1 like 1–platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα) (T674I) mutant. Sorafenib inhibited the proliferation of FIP1L1-PDGFRα and FIP1L1-PDGFRα(T674I)–transformed Ba/F3 cells and induced apoptosis of the EOL-1 cell line at a low nanomolar concentration. Western blot analysis confirmed that these effects were due to a direct effect on FIP1L1-PDGFRα and FIP1L1-PDGFRα(T674I). Sorafenib was recently approved for the treatment of renal cell carcinoma. Our data suggest that low doses of sorafenib could be efficient for the treatment of FIP1L1-PDGFRA–positive CEL and could be used to overcome resistance to imatinib associated with the T674I mutation.

Abstract 92: Platelet Derived Growth Factor Receptor Alpha Signaling is Required for Cardiac Fibroblast Survival and Proliferation

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Malina J Ivey ◽  
Michelle D Tallquist
Keyword(s):  
Preliminary Data ◽  
Cardiac Fibrosis ◽  
Heart Function ◽  
Cardiac Fibroblasts ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Fibroblast Proliferation ◽  
Artery Ligation ◽  
Developing Heart ◽  
Factor Receptor Alpha

Cardiac fibrosis contributes significantly to heart disease and is a hallmark of decreased cardiac function. Currently, there are no treatments that attenuate fibrosis, but identification of signaling pathways required for fibroblast function would provide some potential targets. PDGFRα is a receptor tyrosine kinase that is required for fibroblast formation in the developing heart, and preliminary data indicates that it is also required for maintenance of resident fibroblasts and expansion of activated fibroblasts after injury. Preliminary experiments demonstrate that loss of PDGFRα expression in adult cardiac fibroblasts results in 50% reduction in the number of the resident fibroblasts by 4 days after gene deletion. This was further validated using an independent fibroblast marker, collagen1a1GFP. Based on the low basal level of fibroblast proliferation, we hypothesize that PDGFRα signaling is essential for fibroblast survival and that fibroblasts undergo rapid turnover in the absence of PDGFRα signaling. Future studies will determine the exact mechanism of this loss. We have also begun to elucidate which PDGFRα downstream signals promote fibroblast maintenance. Using a PDGFRα-dependent-PI3K-deficient mouse model, preliminary data indicates that PDGFRα-dependent PI3K signaling is essential for cell survival. We are also investigating the role of PDGFRα signaling after myocardial infarction. Using recently described genetic tools to follow fibroblasts after injury, we have determined that fibroblasts reach their peak of proliferation within a week after permanent left anterior descending artery ligation. This injury-induced proliferation is reduced by 50% after deletion of PDGFRα. Therefore, we have demonstrated that PDGFRα has a role in fibroblast maintenance in the healthy heart, as well as a role in fibroblast proliferation after injury. Our studies will continue to illuminate additional roles for PDGFRα in the fibroblast, as well as the implications of fibroblast loss on other cell types and overall heart function.

Infection and immunity

2021 ◽  
pp. 853-920
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune System ◽  
Cell Types ◽  
The Body ◽  
Acquired Immunity ◽  
Histocompatibility Complex ◽  
Repair Mechanisms ◽  
Antigen Presenting ◽  
Different Cell Types

‘Infection and immunity’ considers the response of the body to pathogens, such as bacteria, viruses, prions, fungi, and parasites, which are discussed in terms of their nature, life cycle, and modes of infection. The role of the immune system in defence against infection is discussed, including innate and adaptive (acquired) immunity, antigens, the major histocompatibility complex, and the different cell types involved (antigen-presenting cells, T-cells, and B-cells). The mechanisms and cellular basis of inflammation are considered, as are post-infection repair mechanisms, and pathologies of the immune system such as hypersensitivity, autoimmunity and transplantations, and immunodeficiency (both primary and secondary to other diseases).

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