scholarly journals Roles and action mechanisms of WNT4 in cell differentiation and human diseases: a review

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Quanlong Zhang ◽  
Yan Pan ◽  
Jingjing Ji ◽  
Yuxin Xu ◽  
Qiaoyan Zhang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Current Knowledge ◽  
Cell Types ◽  
Human Diseases ◽  
Signal Pathways ◽  
Decidual Cell ◽  
Bone Homeostasis ◽  
Cellular Processes ◽  
Development And Differentiation ◽  
And Function

AbstractWNT family member 4 (WNT4), which belongs to the conserved WNT protein family, plays an important role in the development and differentiation of many cell types during the embryonic development and adult homeostasis. Increasing evidence has shown that WNT4 is a special ligand that not only activates the β-catenin independent pathway but also acts on β-catenin signaling based on different cellular processes. This article is a summary of the current knowledge about the expression, regulation, and function of WNT4 ligands and their signal pathways in cell differentiation and human disease processes. WNT4 is a promoter in osteogenic differentiation in bone marrow stromal cells (BMSCs) by participating in bone homeostasis regulation in osteoporotic diseases. Non-canonical WNT4 signaling is necessary for metabolic maturation of pancreatic β-cell. WNT4 is also necessary for decidual cell differentiation and decidualization, which plays an important role in preeclampsia. WNT4 promotes neuronal differentiation of neural stem cell and dendritic cell (DC) into conventional type 1 DC (cDC1). Besides, WNT4 mediates myofibroblast differentiation in the skin, kidney, lung, and liver during scarring or fibrosis. On the negative side, WNT4 is highly expressed in cancer tissues, playing a pro-carcinogenic role in many cancer types. This review provides an overview of the progress in elucidating the role of WNT4 signaling pathway components in cell differentiation in adults, which may provide useful clues for the diagnosis, prevention, and therapy of human diseases.

Abstract P351: The Post-transcriptional Regulations Of Centrosomal Plp Mrna In Drosophila

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Junnan Fang
Keyword(s):  
Translational Control ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cell Types ◽  
Mrna Localization ◽  
Rna Localization ◽  
Embryonic Lethality ◽  
Cellular Processes ◽  
Pericentriolar Material ◽  
And Function

Centrosomes, functioning as microtubule organizing centers, are composed of a proteinaceous matrix of pericentriolar material (PCM) that surrounds a pair of centrioles. Drosophila Pericentrin (Pcnt)-like protein (PLP) is a key component of the centrosome that serves as a scaffold for PCM assembly. The disruption of plp in Drosophila results in embryonic lethality, while the deregulation of Pcnt in humans is associated with MOPD II and Trisomy 21.We recently found plp mRNA localizes to Drosophila embryonic centrosomes. While RNA is known to associate with centrosomes in diverse cell types, the elements required for plp mRNA localization to centrosomes remains completely unknown. Additionally, how plp translation is regulated to accommodate rapid cell divisions during early embryogenesis is unclear. RNA localization coupled with translational control is a conserved mechanism that functions in diverse cellular processes. Control of mRNA localization and translation is mediated by RNA-binding proteins (RBPs). We find PLP protein expression is specifically promoted by an RNA-binding protein, Orb, during embryogenesis; moreover, plp mRNA interacts with Orb. Importantly, we find overexpression of full-length PLP can rescue cell division defects and embryonic lethality caused by orb depletion. We aim to uncover the mechanisms underlying embryonic plp mRNA localization and function and how Orb regulates plp translation.

scholarly journals Human Neural Stem Cell Systems to Explore Pathogen-Related Neurodevelopmental and Neurodegenerative Disorders

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1893
Author(s):  
Matteo Baggiani ◽  
Maria Teresa Dell’Anno ◽  
Mauro Pistello ◽  
Luciano Conti ◽  
Marco Onorati
Keyword(s):  
Extended Period ◽  
Cell Types ◽  
Coxsackie Virus ◽  
Long Term Effects ◽  
Cellular Processes ◽  
Normal Human ◽  
Neuronal Lineage ◽  
Simplex Virus ◽  
And Function ◽  
New Evidence

Building and functioning of the human brain requires the precise orchestration and execution of myriad molecular and cellular processes, across a multitude of cell types and over an extended period of time. Dysregulation of these processes affects structure and function of the brain and can lead to neurodevelopmental, neurological, or psychiatric disorders. Multiple environmental stimuli affect neural stem cells (NSCs) at several levels, thus impairing the normal human neurodevelopmental program. In this review article, we will delineate the main mechanisms of infection adopted by several neurotropic pathogens, and the selective NSC vulnerability. In particular, TORCH agents, i.e., Toxoplasma gondii, others (including Zika virus and Coxsackie virus), Rubella virus, Cytomegalovirus, and Herpes simplex virus, will be considered for their devastating effects on NSC self-renewal with the consequent neural progenitor depletion, the cellular substrate of microcephaly. Moreover, new evidence suggests that some of these agents may also affect the NSC progeny, producing long-term effects in the neuronal lineage. This is evident in the paradigmatic example of the neurodegeneration occurring in Alzheimer’s disease.

scholarly journals The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

2020 ◽  
Author(s):  
Guoxia Wen ◽  
Tong Zhou ◽  
Wanjun Gu
Keyword(s):  
Liquid Biopsy ◽  
Developmental Stages ◽  
Current Knowledge ◽  
Cell Types ◽  
Circular Rna ◽  
Disease Diagnosis ◽  
Human Diseases ◽  
Biological Functions ◽  
Aberrant Expression ◽  
Physiological Processes

Abstract Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.

Generation of Free Radicals and Messenger Function

1995 ◽  
Vol 20 (3) ◽  
pp. 280-288 ◽  
Author(s):  
John C. Carlson ◽  
Masaaki Sawada
Keyword(s):  
Free Radicals ◽  
Cell Function ◽  
Control Cell ◽  
Muscle Cells ◽  
Cell Types ◽  
Signal Pathways ◽  
Cellular Processes ◽  
Toxic Agents ◽  
Intracellular Messengers ◽  
Antioxidant Mechanisms

Free radicals are toxic agents that are produced as by-products of metabolic activity. A number of antioxidant mechanisms work to protect cells from damage. Recent evidence indicates, however, that free radicals and related oxidants such as hydrogen peroxide may also have a beneficial role, working as messengers to control cell function. These agents are generated in response to agonists, production is regulated by intracellular signal pathways, and they appear to be used to control particular cellular processes. Free radicals may perform these functions in a number of cell types. Also, they are produced in muscles and there is evidence that they may work as messengers in smooth muscle cells. Key words: phospholipases, intracellular messengers, regulation of function, muscle cells

scholarly journals Mitochondrial Heterogeneity in the Brain at the Cellular Level

1998 ◽  
Vol 18 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Ursula Sonnewald ◽  
Leif Hertz ◽  
Arne Schousboe
Keyword(s):  
Amino Acid ◽  
Current Knowledge ◽  
Cell Types ◽  
Cellular Level ◽  
Mitochondrial Structure ◽  
Cell Type Specific ◽  
Mitochondrial Heterogeneity ◽  
Specific Tissue ◽  
And Function ◽  
The Brain

Classically, compartmentation of glutamate metabolism in the brain is associated with the fact that neurons and glia exhibit distinct differences with regard to metabolism of this amino acid. The recent use of 13C-labeled compounds to study this metabolism in conjunction with the availability of cell type-specific tissue culture modes has led to the notion that such compartmentation may even be present in individual cell types, neurons as well as glia. To better understand and explain this, it is proposed that mitochondrial heterogeneity may exist resulting in tricarboxylic acid cycles with different properties regarding cycling rates and ratio as well as coupling to amino acid biosynthesis, primarily involving glutamate and aspartate. These hypotheses are evaluated in the light of current knowledge about mitochondrial structure and function.

scholarly journals Inhibins Tune the Thymocyte Selection Process by Regulating Thymic Stromal Cell Differentiation

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Ebzadrel Carbajal-Franco ◽  
Marisol de la Fuente-Granada ◽  
Germán R. Alemán-Muench ◽  
Eduardo A. García-Zepeda ◽  
Gloria Soldevila
Keyword(s):  
Cell Differentiation ◽  
Mhc Class Ii ◽  
Stromal Cell ◽  
Selection Process ◽  
Cell Types ◽  
Smad Proteins ◽  
Thymocyte Differentiation ◽  
And Function ◽  
T Cell Selection ◽  
Selection Of

Inhibins and Activins are members of the TGF-βsuperfamily that regulate the differentiation of several cell types. These ligands were initially identified as hormones that regulate the hypothalamus-pituitary-gonadal axis; however, increasing evidence has demonstrated that they are key regulators in the immune system. We have previously demonstrated that Inhibins are the main Activin ligands expressed in the murine thymus and that they regulate thymocyte differentiation, promoting the DN3-DN4 transition and the selection of SP thymocytes. As Inhibins are mainly produced by thymic stromal cells, which also express Activin receptors and Smad proteins, we hypothesized that Inhibins might play a role in stromal cell differentiation and function. Here, we demonstrate that, in the absence of Inhibins, thymic conventional dendritic cells display reduced levels of MHC Class II (MHCII) and CD86. In addition, the ratio between cTECs and mTECs was affected, indicating that mTEC differentiation was favoured and cTEC diminished in the absence of Inhibins. These changes appeared to impact thymocyte selection leading to a decreased selection of CD4SP thymocytes and increased generation of natural regulatory T cells. These findings demonstrate that Inhibins tune the T cell selection process by regulating both thymocyte and stromal cell differentiation.

scholarly journals Hypoxia. 4. Hypoxia and ion channel function

2011 ◽  
Vol 300 (5) ◽  
pp. C951-C967 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Jan Polak
Keyword(s):  
Ion Channels ◽  
Cell Function ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Cell Types ◽  
Cellular Processes ◽  
Oxygen Sensitive ◽  
Sense And Respond ◽  
And Function ◽  
And Control

The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes.

scholarly journals Glioendocrine System: Effects of Thyroid Hormones in Glia and their Functions in the Central Nervous System

2020 ◽  
Vol 3 (1) ◽  
pp. 1-11
Author(s):  
Mami Noda
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Impairment ◽  
Thyroid Hormones ◽  
Glial Cells ◽  
Endocrine System ◽  
Cell Types ◽  
Development And Differentiation ◽  
The Central Nervous System ◽  
And Function

AbstractGlial cells play a significant role in the link between the endocrine and nervous systems. Among hormones, thyroid hormones (THs) are critical for the regulation of development and differentiation of neurons and glial cells, and hence for development and function of the central nervous system (CNS). THs are transported into the CNS, metabolized in astrocytes and affect various cell types in the CNS including astrocyte itself. Since 3,3’,5-triiodo-L-thyronine (T3) is apparently released from astrocytes in the CNS, it is a typical example of glia-endocrine system.The prevalence of thyroid disorders increases with age. Both hypothyroidism and hyperthyroidism are reported to increase the risk of cognitive impairment or Alzheimer’s disease (AD). Therefore, understanding the neuroglial effects of THs may help to solve the problem why hypothyroidism or hyperthyroidism may cause mental disorders or become a risk factor for cognitive impairment. In this review, THs are focused among wide variety of hormones related to brain function, and recent advancement in glioendocrine system is described.

scholarly journals The story of the fibrin(ogen) αC-domains: evolution of our view on their structure and interactions

2021 ◽  
Author(s):  
Leonid Medved ◽  
John W Weisel
Keyword(s):  
Binding Sites ◽  
Current Knowledge ◽  
Optical Trap ◽  
Cell Types ◽  
Ordered Structures ◽  
Multiple Binding Sites ◽  
New Information ◽  
Multiple Binding ◽  
And Function ◽  
Fibrinogen Molecule

Although much has been established concerning the overall structure and function of fibrinogen, much less has been known about its two αC regions, each consisting of an αC-connector and αC-domain, but new information has been accumulating. This review summarizes the state of our current knowledge of the structure and interactions of fibrinogen’s αC regions. A series of studies with isolated αC regions and their fragments demonstrated that the αC-domain forms compact ordered structures consisting of N- and C-terminal sub-domains including β sheets and suggested that the αC-connector has a poly(L-proline) type II structure. Functionally, the αC-domains interact intramolecularly with each other and with the central region of the molecule, first demonstrated by electron microscopy and then quantified by optical trap force spectroscopy. Upon conversion of fibrinogen into fibrin, the αC-domains switch from intra- to intermolecular interactions to form ordered αC polymers. The formation of αC polymers occurs mainly through the homophilic interaction between the N-terminal sub-domains; interaction between the C-terminal sub-domains and the αC-connectors also contributes to this process. Considerable evidence supports the idea that the αC-regions accelerate fibrin polymerization and affect the final structure of fibrin clots. The interactions between αC-regions are important for the mechanical properties of clots, increasing their stiffness and extensibility. Conversion of fibrinogen into fibrin results in exposure of multiple binding sites in its αC regions, providing interaction of fibrin with different proteins and cell types during hemostasis and wound healing. This heretofore mysterious part of the fibrinogen molecule is finally giving up its secrets.

scholarly journals Neonatal Fc receptor (FcRn) – not only transporter of maternal IgG

2018 ◽  
Vol 72 ◽  
pp. 701-727
Author(s):  
Joanna E. Mikulska
Keyword(s):  
Mhc Class I ◽  
Current Knowledge ◽  
Cell Types ◽  
Fc Receptor ◽  
Class I ◽  
Neonatal Fc Receptor ◽  
The Status ◽  
And Function ◽  
Different Cell Types ◽  
Maternal Igg

The neonatal Fc receptor, (FcRn) is a transmembrane, heterodimeric glycoprotein with a structure similar to MHC class I molecules. In contrast to MHC class I antigens, FcRn does not bind to peptides (antigens) but interacts with the Fc fragment of IgG and albumin. The FcRn-IgG interaction as well as the FcRn-albumin interaction occur at acidic pH (optimally at pH 5.0-6.5) but not in physiological environment. These two ligands bind to distinct binding sites on the receptor molecule and by different mechanisms. Now, it is known that the expression of FcRn is not restricted to sites involved in the transport of maternal IgG, and this receptor is not responsible only for transfer the passive immunity from mother to the offspring. But FcRn has a much broader range of expression and function, throughout life and in many different cell types and tissues of humans and animals. This review summarizes the status of our knowledge on the expression, interaction with ligands and functions of the neonatal Fc receptor. This article shows also the possibilities of utilizing a current knowledge on FcRn for therapeutic purposes.

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