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Recent in vitro Models for the Blood-Brain Barrier
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
João Basso, Maria Mendes, Maria Ferreira, João Sousa, Alberto Pais, Carla Vitorino
As previously mentioned, microfluidic models are extremely versatile and may also contemplate the culture of other cells of the neurovascular units, thus representing a more reliable physiological state. Astrocytes are star-shaped glial cells which perform different tasks in the CNS, including the biochemical support to the endothelial cells, the secretion of cellular growth substances (growth factors, cytokines and ECM proteins) for the BBB function and assistance in the transport regulation across the capillaries. The close contact with endothelial cells suggests that astrocytes are crucial for the development of BBB, and their differentiation is linked with the BBB maturation. Pericytes are found in the walls of the capillaries and are essential to the control of blood flow in cerebral vessels. Pericytes synthesise elements necessary for the differentiation of the BBB as beta-type platelet-derived growth factor receptor (PDGFRb) and the proteoglycan neural/glial antigen 2 (NG2). Neurons are the main component of the brain and are in direct contact with endothelial cells and astrocytes. They are accountable for the degree of BBB permeability and the control of blood flow, as the presence of neurons increases the barrier effects. Microglia are innate immune cells in the CNS and have an important role in maintaining the function and the integrity of the BBB. For example, the activation of macrophages is one of the marks of an infected brain and suggests that the effectiveness of the barrier is compromised.
Introduction to Oral and Craniofacial Tissue Engineering
Published in Vincenzo Guarino, Marco Antonio Alvarez-Pérez, Current Advances in Oral and Craniofacial Tissue Engineering, 2020
María Verónica Cuevas González, Eduardo Villarreal-Ramírez, Adriana Pérez-Soria, Pedro Alberto López Reynoso, Vincenzo Guarino, Marco Antonio Alvarez-Pérez
Platelet-Derived Growth Factor (PDGF) is a soluble protein has reported four additional forms (PDGFa, PDGFb, PDGFc, PDGFd) a cystine knit motif characterizes this family of proteins and its function depends on its self-association in homodimers (AA, BB, CC, DD) and heterodimers (AB). The signaling mechanism of the five isoforms of PDGF depends on the interaction with some of the two receptors PDGFRα and PDGFRβ. Platelets are composed of multiple storage granules, i.e., lysosomes and alpha granules which are delivered after its activation (coagulation), through this process of degranulation PDGF is released and performs its function locally in an autocrine fashion or in other tissues such as a paracrine mode. The cellular mechanism described for the PDGF associated with periodontium regeneration involves binding to the cell membrane tyrosine kinase receptors and subsequently exerts the activation of its effects on chemotaxis, cell proliferation, migration, extracellular matrix synthesis and anti-apoptosis via the Rac GTPase which modulates the actin cytoskeleton and the lamellopodia formation (Trofin et al. 2013; McGuire et al. 2006; Mellonig et al. 2009).
Protein Function As Cell Surface And Nuclear Receptor In Human Diseases
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Urmila Jarouliya, Raj K. Keservani
This factor was purified by Heldin et al. in the mid-1970s; several other researcher groups demonstrated the existence of a major serum growth factor for fibroblasts, smooth muscle cells and glial cells, all are derived from platelets. This factor was further known as a platelet-derived growth factor (PDGF). PDGF receptor for PDGFs is a receptor tyrosine kinase and is made up of by PDGFRα and PDGFRβ. PDGFs are highly expressed in the heart, skeletal muscle, pancreas and moderate levels in other organs. PDGF family stimulates the proliferation, survival, and motility of connective tissue cells and certain other cell types. PDGF isoforms have important roles during the embryonal development, particularly to promote the development of various mesenchymal cell types in different organs [58]. In the adult, PDGF stimulates normal wound healing [59] and regulates the interstitial fluid pressure (IFP) of tissues [60].
A PDGFRB- and CD40-targeting bispecific AffiMab induces stroma-targeted immune cell activation
Published in mAbs, 2023
Alessandro Mega, Aman Mebrahtu, Gustav Aniander, Eva Ryer, Annette Sköld, Anna Sandegren, Eva Backström Rydin, Johan Rockberg, Arne Östman, Fredrik Y. Frejd
Platelet-derived growth factor receptor beta (PDGFRB) is expressed in the stroma of several types of cancer. Higher expression has been associated with poorer prognosis in various cancer types.18–20 The signaling axis involving PDGFRs and their ligands has been shown to be essential for the contribution of CAFs to several hallmarks of cancer, including proliferation, migration, and response to treatment.19 Recently, a set of studies have corroborated the importance of PDGFRB as a stromal marker by associating the presence of PDGFRB+ cells in the tumor stroma and subsets of PDGFRB+ CAFs with modulation of radiosensitivity of cancer cells,21 survival,22 disease recurrence,23 and immune features.24 Hence, PDGFRB displays properties making it an attractive tumor stroma target to explore.
Determination of cytokine profile and associated genes of the signaling pathway in HNSCC
Published in Journal of Receptors and Signal Transduction, 2022
Aysel Kalayci Yigin, Ali Azzawri, Kayhan Ozturk, Tulin Cora, Mehmet Seven
PDGFRB, a homodimer of PDGFB, is associated with a poor prognosis of many common malignancies especially fibroblast-rich stroma [20], and it is also a crucial factor for tumor growth, angiogenesis and tumor survival. PDGFRB has been found to interact with members of several different RTK families, including EGFR [21]. PTEN is an important tumor suppressor gene, which functions in many cellular processes such as cell proliferation, survival, growth, metabolism, cell migration by inactivating PI3-kinase-dependent signaling. In the literature, associations between PTEN and PDGF isoforms were reported in human prostate cancer cell lines [22]. Lin et al. reported that the expressions of PDGFA and PDGFB mRNAs were higher in oral squamose cell carcinoma tissue than in the adjacent normal tissues [23]. Taken together, our results suggest a mechanism by which loss of PTEN may promote HNSCC progression via PDGFR signal transduction in HNSCC.
Endostatin in fibrosis and as a potential candidate of anti-fibrotic therapy
Published in Drug Delivery, 2021
Zequn Zhang, Xi Liu, Zhaolong Shen, Jun Quan, Changwei Lin, Xiaorong Li, Gui Hu
Platelet-derived growth factor (PDGF) is a major mitogenic agent. There are five PDGF subtypes: PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, and PDGF-DD. PDGF receptor (PDGFR) is a transmembrane glycoprotein with tyrosine-protein kinase activity, including three kinds of dimers, αα, αβ, and ββ, which are composed of PDGF-α and PDGFR-β subunits in a certain way. PDGF-A and PDGF-C predominantly bind to PDGFR-α chain, PDGF-B binds to both -α and -β chains, and PDGF-D binds to the β chain only. PDGF functions depend not just on the concentration of the ligand but also on ligand binding to specific receptors. Mesenchymal cells are the principal site of PDGFRs expression. Once bound by ligands, PDGFRs are phosphorylated to activate transcription factors and diverse cytoplasmic signaling cascades, like Janus kinase, mitogen-activated protein kinase, p38, phospholipase C, and Ras GTPase activating protein, driving downstream gene expression and exerting biological effects (De Donatis et al. 2008; Klinkhammer et al. 2018; Papadopoulos & Lennartsson 2018; Sil et al. 2018).