Mechanoactivation of Wnt/β-catenin pathways in health and disease

2018 ◽  
Vol 2 (5) ◽  
pp. 701-712 ◽  
Author(s):  
Christina M. Warboys
Keyword(s):  
Cardiovascular Disease ◽  
Wnt Pathway ◽  
Mechanical Strain ◽  
Cell Types ◽  
Mechanical Forces ◽  
Lymphatic Endothelium ◽  
Canonical Pathways ◽  
Health And Disease ◽  
Multiple Cell ◽  
Sense And Respond

Mechanical forces play an important role in regulating tissue development and homeostasis in multiple cell types including bone, joint, epithelial and vascular cells, and are also implicated in the development of diseases, e.g. osteoporosis, cardiovascular disease and osteoarthritis. Defining the mechanisms by which cells sense and respond to mechanical forces therefore has important implications for our understanding of tissue function in health and disease and may lead to the identification of targets for therapeutic intervention. Mechanoactivation of the Wnt signalling pathway was first identified in osteoblasts with a key role for β-catenin demonstrated in loading-induced osteogenesis. Since then, mechanoregulation of the Wnt pathway has also been observed in stem cells, epithelium, chondrocytes and vascular and lymphatic endothelium. Wnt can signal through both canonical and non-canonical pathways, and evidence suggests that both can mediate responses to mechanical strain, stretch and shear stress. This review will discuss our current understanding of the activation of the Wnt pathway in response to mechanical forces.

Adipokines and the cardiovascular system: mechanisms mediating health and disease

2012 ◽  
Vol 90 (8) ◽  
pp. 1029-1059 ◽  
Author(s):  
Josette M. Northcott ◽  
Azadeh Yeganeh ◽  
Carla G. Taylor ◽  
Peter Zahradka ◽  
Jeffrey T. Wigle
Keyword(s):  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Cardiovascular System ◽  
Cardiac Fibroblasts ◽  
Tissue Expansion ◽  
Cell Types ◽  
Vessel Growth ◽  
Major Cell Type ◽  
Health And Disease ◽  
Cardiovascular Cells

This review focuses on the role of adipokines in the maintenance of a healthy cardiovascular system, and the mechanisms by which these factors mediate the development of cardiovascular disease in obesity. Adipocytes are the major cell type comprising the adipose tissue. These cells secrete numerous factors, termed adipokines, into the blood, including adiponectin, leptin, resistin, chemerin, omentin, vaspin, and visfatin. Adipose tissue is a highly vascularised endocrine organ, and different adipose depots have distinct adipokine secretion profiles, which are altered with obesity. The ability of many adipokines to stimulate angiogenesis is crucial for adipose tissue expansion; however, excessive blood vessel growth is deleterious. As well, some adipokines induce inflammation, which promotes cardiovascular disease progression. We discuss how these 7 aforementioned adipokines act upon the various cardiovascular cell types (endothelial progenitor cells, endothelial cells, vascular smooth muscle cells, pericytes, cardiomyocytes, and cardiac fibroblasts), the direct effects of these actions, and their overall impact on the cardiovascular system. These were chosen, as these adipokines are secreted predominantly from adipocytes and have known effects on cardiovascular cells.

scholarly journals Periodontal cell mechanotransduction

Open Biology ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 180053 ◽  
Author(s):  
Sasanka S. Chukkapalli ◽  
Tanmay P. Lele
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Periodontal Disease ◽  
Significant Role ◽  
Cell Types ◽  
Mechanical Stresses ◽  
Mechanical Forces ◽  
Biological Processes ◽  
Cellular Mechanisms ◽  
Health And Disease

The periodontium is a structurally and functionally complex tissue that facilitates the anchorage of teeth in jaws. The periodontium consists of various cell types including stem cells, fibroblasts and epithelial cells. Cells of the periodontium are constantly exposed to mechanical stresses generated by biological processes such as the chewing motions of teeth, by flows generated by tongue motions and by forces generated by implants. Mechanical stresses modulate the function of cells in the periodontium, and may play a significant role in the development of periodontal disease. Here, we review the literature on the effect of mechanical forces on periodontal cells in health and disease with an emphasis on molecular and cellular mechanisms.

scholarly journals Single-cell transcriptomics to explore the immune system in health and disease

Science ◽  
2017 ◽  
Vol 358 (6359) ◽  
pp. 58-63 ◽  
Author(s):  
Michael J. T. Stubbington ◽  
Orit Rozenblatt-Rosen ◽  
Aviv Regev ◽  
Sarah A. Teichmann
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Immune Cells ◽  
Cell Types ◽  
Massively Parallel ◽  
Antigen Receptors ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Health And Disease ◽  
Multiple Cell

The immune system varies in cell types, states, and locations. The complex networks, interactions, and responses of immune cells produce diverse cellular ecosystems composed of multiple cell types, accompanied by genetic diversity in antigen receptors. Within this ecosystem, innate and adaptive immune cells maintain and protect tissue function, integrity, and homeostasis upon changes in functional demands and diverse insults. Characterizing this inherent complexity requires studies at single-cell resolution. Recent advances such as massively parallel single-cell RNA sequencing and sophisticated computational methods are catalyzing a revolution in our understanding of immunology. Here we provide an overview of the state of single-cell genomics methods and an outlook on the use of single-cell techniques to decipher the adaptive and innate components of immunity.

Flow increases superoxide production by NADPH oxidase via activation of Na-K-2Cl cotransport and mechanical stress in thick ascending limbs

2007 ◽  
Vol 292 (3) ◽  
pp. F993-F998 ◽  
Author(s):  
Nancy J. Hong ◽  
Jeffrey L. Garvin
Keyword(s):  
Nadph Oxidase ◽  
Mechanical Stress ◽  
Mechanical Strain ◽  
Cell Types ◽  
Mechanical Forces ◽  
Free Solution ◽  
Luminal Flow ◽  
Mechanical Factors ◽  
Tubular Flow ◽  
Isolated Rat

Superoxide (O2−) regulates renal function and is implicated in hypertension. O2− production increases in response to increased ion delivery in thick ascending limbs (TALs) and macula densa and mechanical strain in other cell types. Tubular flow in the kidney acutely varies causing changes in ion delivery and mechanical stress. We hypothesized that increasing luminal flow stimulates O2− production by NADPH oxidase in TALs via activation of Na-K-2Cl cotransport. We measured intracellular O2− in isolated rat TALs using dihydroethidium in the presence and absence of luminal flow and inhibitors of NADPH oxidase, Na-K-2Cl cotransport, and Na/H exchange. In the absence of flow, the rate of O2− production was 5.8 ± 1.4 AU/s. After flow was initiated, it increased to 29.7 ± 4.3 AU/s ( P < 0.001). O2− production was linearly related to flow. Tempol alone and apocynin alone blocked the flow-induced increase in O2− production (3.5 ± 1.7 vs. 4.5 ± 2.8 AU/s and 8.2 ± 2.1 vs. 10.6 ± 2.8 AU/s, respectively). Furosemide decreased flow-induced O2− production by 55% (37.3 ± 5.2 to 16.8 ± 2.8 AU/s; P < 0.002); however, dimethylamiloride had no effect. Finally, we examined whether changes in mechanical forces are involved in flow-induced O2− production by using a Na-free solution to perfuse TALs. In the absence of NaCl, luminal flow enhanced O2− production (1.5 ± 0.5 to 13.5 ± 1.1 AU/s; P < 0.001), ∼50% less stimulation than when flow was increased in the presence of luminal NaCl. We conclude that flow stimulates O2− production in TALs via activation of NADPH oxidase and that NaCl absorption due to Na-K-2Cl cotransport and flow-associated mechanical factors contribute equally to this process.

scholarly journals MicroRNAs as Therapeutic Targets and Clinical Biomarkers in Atherosclerosis

2019 ◽  
Vol 8 (12) ◽  
pp. 2199 ◽  
Author(s):  
Emma L. Solly ◽  
Catherine G. Dimasi ◽  
Christina A. Bursill ◽  
Peter J. Psaltis ◽  
Joanne T. M. Tan
Keyword(s):  
Cardiovascular Disease ◽  
Therapeutic Targets ◽  
Holistic Approach ◽  
Cell Types ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cellular Mechanisms ◽  
Cellular Effects ◽  
Clinical Biomarkers ◽  
Current Therapies ◽  
Multiple Cell

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Atherosclerosis develops over several decades and is mediated by a complex interplay of cellular mechanisms that drive a chronic inflammatory milieu and cell-to-cell interactions between endothelial cells, smooth muscle cells and macrophages that promote plaque development and progression. While there has been significant therapeutic advancement, there remains a gap where novel therapeutic approaches can complement current therapies to provide a holistic approach for treating atherosclerosis to orchestrate the regulation of complex signalling networks across multiple cell types and different stages of disease progression. MicroRNAs (miRNAs) are emerging as important post-transcriptional regulators of a suite of molecular signalling pathways and pathophysiological cellular effects. Furthermore, circulating miRNAs have emerged as a new class of disease biomarkers to better inform clinical diagnosis and provide new avenues for personalised therapies. This review focusses on recent insights into the potential role of miRNAs both as therapeutic targets in the regulation of the most influential processes that govern atherosclerosis and as clinical biomarkers that may be reflective of disease severity, highlighting the potential theranostic (therapeutic and diagnostic) properties of miRNAs in the management of cardiovascular disease.

scholarly journals Prohibitin: A hypothetical target for sex-based new therapeutics for metabolic and immune diseases

2019 ◽  
Vol 244 (2) ◽  
pp. 157-170 ◽  
Author(s):  
Suresh Mishra ◽  
BL Grégoire Nyomba
Keyword(s):  
Sex Differences ◽  
Sex Steroids ◽  
Immune Cell ◽  
Cell Types ◽  
Immune Functions ◽  
Evolutionarily Conserved ◽  
Health And Disease ◽  
Multiple Cell ◽  
Membrane Signaling

Adipose and immune functions display sex differences and are influenced by sex steroid hormones in health and disease. However, effector molecules that mediate the effects of sex steroids and determine sex differences in adipocytes and immune cells are largely unknown. Sex differences are known to exist in mitochondrial biology, and mitochondria play a crucial role in adipocyte and immune cell functions. In fact, mitochondrial dysregulation is a common finding in a number of diseases that exhibit sex differences. It is, therefore, possible that mitochondria carry out sex-dimorphic functions. Prohibitin, an evolutionarily conserved pleiotropic protein, known to function as a mitochondrial chaperone, has multifaceted relationship with sex steroids and their receptors. New evidence indicates that prohibitin has roles in sex differences in multiple cell and tissue types, including adipocytes, macrophages, and dendritic cells. Transgenic mice overexpressing prohibitin in adipocytes, macrophages, and dendritic cells exhibit sex differences in metabolic and immune phenotypes, mediated through mitochondrial and plasma membrane signaling functions of prohibitin. Thus, the discovery of prohibitin as mediating the effects of sex steroids in multiple cell types has opened a new research direction to study the relationship between sex steroids and mitochondrial proteins and their impact on sex differences in health and disease. In this opinion article, we will provide a personal perspective of the role of prohibitin with cellular compartment- and tissue-specific functions in mediating sex-dimorphic adipose and immune functions. We believe that prohibitin is a potential target for sex-based new therapeutics for metabolic and immune diseases. Impact statement Traditional sex-related biases in research are now obsolete, and it is important to identify the sex of humans, animals, and even cells in research protocols, due to the role of sex as a fundamental facet of biology, predisposition to disease, and response to therapy. Genetic sex, epigenetics and hormonal regulations, generate sex-dimorphisms. Recent investigations acknowledge sex differences in metabolic and immune health as well as chronic diseases. Prohibitin, an evolutionarily conserved molecule, has pleotropic functions in mitochondrial housekeeping, plasma membrane signaling, and nuclear genetic transcription. Studies in adipocytes, macrophages, and transgenic mice indicate that prohibitin interacts with sex steroids and plays a role in mediating sex differences in adipose tissues and immune cell types. Prohibitin may, depending on context, modulate predisposition to chronic metabolic diseases and malignancy and, because of these attributes, could be a target for sex-based therapies of metabolic and immune-related diseases as well as cancer.

scholarly journals The Role of Exosomes in Bone Remodeling: Implications for Bone Physiology and Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Christos Masaoutis ◽  
Stamatios Theocharis
Keyword(s):  
Bone Remodeling ◽  
Current Knowledge ◽  
Active Role ◽  
Cell Types ◽  
Matrix Mineralization ◽  
Physiological Phenomenon ◽  
Health And Disease ◽  
Multiple Cell ◽  
Bone Physiology

Bone remodeling represents a physiological phenomenon of continuous bone tissue renewal that requires fine orchestration of multiple cell types, which is critical for the understanding of bone disease but not yet clarified in precise detail. Exosomes, which are cell-secreted nanovesicles drawing increasing attention for their broad biosignaling functions, can shed new light on how multiple heterogeneous cells communicate for the purpose of bone remodeling. In the healthy bone, exosomes transmit signals favoring both bone synthesis and resorption, regulating the differentiation, recruitment, and activity of most cell types involved in bone remodeling and even assuming an active role in extracellular matrix mineralization. Additionally, in the ailing bone, they actively participate in pathogenic processes constituting also potential therapeutic agents and drug vectors. The present review summarizes the current knowledge on bone exosomes and bone remodeling in health and disease.

scholarly journals Imaging and Manipulating Pituitary Function in the Awake Mouse

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2271-2281 ◽  
Author(s):  
Ombeline Hoa ◽  
Chrystel Lafont ◽  
Pierre Fontanaud ◽  
Anne Guillou ◽  
Yasmine Kemkem ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Cell Types ◽  
Temporal Regulation ◽  
Hypothalamic Regulation ◽  
Health And Disease ◽  
Multiple Cell ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain

Abstract Extensive efforts have been made to explore how the activities of multiple brain cells combine to alter physiology through imaging and cell-specific manipulation in different animal models. However, the temporal regulation of peripheral organs by the neuroendocrine factors released by the brain is poorly understood. We have established a suite of adaptable methodologies to interrogate in vivo the relationship of hypothalamic regulation with the secretory output of the pituitary gland, which has complex functional networks of multiple cell types intermingled with the vasculature. These allow imaging and optogenetic manipulation of cell activities in the pituitary gland in awake mouse models, in which both neuronal regulatory activity and hormonal output are preserved. These methodologies are now readily applicable for longitudinal studies of short-lived events (e.g., calcium signals controlling hormone exocytosis) and slowly evolving processes such as tissue remodeling in health and disease over a period of days to weeks.

scholarly journals MicroRNAs: Promising New Antiangiogenic Targets in Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sandra Gallach ◽  
Silvia Calabuig-Fariñas ◽  
Eloisa Jantus-Lewintre ◽  
Carlos Camps
Keyword(s):  
Cell Types ◽  
Biological Processes ◽  
Tumour Angiogenesis ◽  
Proliferation And Apoptosis ◽  
Sequence Complementarity ◽  
Specific Proteins ◽  
Health And Disease ◽  
Multiple Cell ◽  
Non Coding Rnas

MicroRNAs are one class of small, endogenous, non-coding RNAs that are approximately 22 nucleotides in length; they are very numerous, have been phylogenetically conserved, and involved in biological processes such as development, differentiation, cell proliferation, and apoptosis. MicroRNAs contribute to modulating the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules and so they play a key role in both health and disease. Angiogenesis is the process of new blood vessel formation from preexisting ones, which is particularly relevant to cancer and its progression. Over the last few years, microRNAs have emerged as critical regulators of signalling pathways in multiple cell types including endothelial and perivascular cells. This review summarises the role of miRNAs in tumour angiogenesis and their potential implications as therapeutic targets in cancer.

scholarly journals The LINC Between Mechanical Forces and Chromatin

2021 ◽  
Vol 12 ◽  
Author(s):  
Olga Lityagina ◽  
Gergana Dobreva
Keyword(s):  
Cardiovascular Disease ◽  
Current Knowledge ◽  
Nuclear Lamina ◽  
Cell Types ◽  
Postnatal Growth ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Linc Complex ◽  
Tensile Forces ◽  
And Function

The heart continually senses and responds to mechanical stimuli that balance cardiac structure and activity. Tensile forces, compressive forces, and shear stress are sensed by the different cardiac cell types and converted into signals instructing proper heart morphogenesis, postnatal growth, and function. Defects in mechanotransduction, the ability of cells to convert mechanical stimuli into biochemical signals, are implicated in cardiovascular disease development and progression. In this review, we summarize the current knowledge on how mechanical forces are transduced to chromatin through the tensed actomyosin cytoskeleton, the linker of nucleoskeleton and cytoskeleton (LINC) complex and the nuclear lamina. We also discuss the functional significance of the LINC complex in cardiovascular disease.

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