scholarly journals Regulation of Epithelial Cell Functions by the Osmolality and Hydrostatic Pressure Gradients: A Possible Role of the Tight Junction as a Sensor

2019 ◽  
Vol 20 (14) ◽  
pp. 3513 ◽  
Author(s):  
Shinsaku Tokuda ◽  
Alan S. L. Yu
Keyword(s):  
Cell Proliferation ◽  
Hydrostatic Pressure ◽  
Tight Junction ◽  
External Environment ◽  
Transepithelial Transport ◽  
Pressure Gradients ◽  
Cell Functions ◽  
Pathological Conditions ◽  
Extracellular Environment

Epithelia act as a barrier to the external environment. The extracellular environment constantly changes, and the epithelia are required to regulate their function in accordance with the changes in the environment. It has been reported that a difference of the environment between the apical and basal sides of epithelia such as osmolality and hydrostatic pressure affects various epithelial functions including transepithelial transport, cytoskeleton, and cell proliferation. In this paper, we review the regulation of epithelial functions by the gradients of osmolality and hydrostatic pressure. We also examine the significance of this regulation in pathological conditions especially focusing on the role of the hydrostatic pressure gradient in the pathogenesis of carcinomas. Furthermore, we discuss the mechanism by which epithelia sense the osmotic and hydrostatic pressure gradients and the possible role of the tight junction as a sensor of the extracellular environment to regulate epithelial functions.

Role of cytoskeleton, cell proliferation and tight junction in wound healing: New therapeutic strategy

2011 ◽  
Vol 205 ◽  
pp. S275
Author(s):  
K. Ghazi ◽  
M. Dutot ◽  
O. Laprévote ◽  
J. Warnet ◽  
P. Rat
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Tight Junction ◽  
Therapeutic Strategy

The tight junction: a multifunctional complex

2004 ◽  
Vol 286 (6) ◽  
pp. C1213-C1228 ◽  
Author(s):  
Eveline E. Schneeberger ◽  
Robert D. Lynch
Keyword(s):  
Tight Junction ◽  
Water Flux ◽  
External Environment ◽  
Integral Membrane Proteins ◽  
Permeability Barrier ◽  
Cell Functions ◽  
Recent Developments ◽  
Junctional Complexes ◽  
Multicellular Organisms ◽  
Short Time

Multicellular organisms are separated from the external environment by a layer of epithelial cells whose integrity is maintained by intercellular junctional complexes composed of tight junctions, adherens junctions, and desmosomes, whereas gap junctions provide for intercellular communication. The aim of this review is to present an updated overview of recent developments in the area of tight junction biology. In a relatively short time, our knowledge of the tight junction has evolved from a relatively simple view of it being a permeability barrier in the paracellular space and a fence in the plane of the plasma membrane to one of it acting as a multicomponent, multifunctional complex that is involved in regulating numerous and diverse cell functions. A group of integral membrane proteins—occludin, claudins, and junction adhesion molecules—interact with an increasingly complex array of tight junction plaque proteins not only to regulate paracellular solute and water flux but also to integrate such diverse processes as gene transcription, tumor suppression, cell proliferation, and cell polarity.

scholarly journals Extracellular matrix endocytosis in controlling matrix turnover and beyond: emerging roles in cancer

2016 ◽  
Vol 44 (5) ◽  
pp. 1347-1354 ◽  
Author(s):  
Elena Rainero
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Secreted Proteins ◽  
Oncogenic Transformation ◽  
Intracellular Degradation ◽  
Cell Functions ◽  
Ecm Degradation

The extracellular matrix (ECM) is a network of secreted proteins that, beyond providing support for tissues and organs, is involved in the regulation of a variety of cell functions, including cell proliferation, polarity, migration and oncogenic transformation. ECM homeostasis is maintained through a tightly controlled balance between synthesis, deposition and degradation. While the role of metalloproteases in ECM degradation is widely recognised, the contribution of ECM internalisation and intracellular degradation to ECM maintenance has been mostly overlooked. In this review, I will summarise what is known about the molecular mechanisms mediating ECM endocytosis and how this process impacts on diseases, such as fibrosis and cancer.

Peripheral nerve as an osmometer: role of the perineurium in frog sciatic nerve

1983 ◽  
Vol 244 (1) ◽  
pp. C75-C81 ◽  
Author(s):  
P. Ask ◽  
H. Levitan ◽  
P. J. Robinson ◽  
S. I. Rapoport
Keyword(s):  
Hydrostatic Pressure ◽  
Sciatic Nerve ◽  
Unit Length ◽  
Elastic Tissue ◽  
A Value ◽  
Pathological Conditions ◽  
Frog Sciatic Nerve ◽  
Pressure Fall

Measurements of volume and hydrostatic pressure in the frog sciatic nerve in vitro demonstrate that the nerve acts as an osmometer, in large part because the perineurium is a semipermeable membrane for water flow. Endoneurial hydrostatic pressure in nerves in isotonic Ringer exceeds bath pressure by about 7 mmHg. In Ringer made hypertonic by addition of sucrose, nerve volume and endoneurial pressure fall linearly in relation to 1/osmolality. The slope of the plot of pressure against volume provides a value for nerve compliance equal to 0.006 mm2/mmHg. Calculations based on the model of the nerve as an osmometer indicate that the nerve has an osmotically "inactive" volume equal to 0.19 mm3/mm, which is about 75% of the total volume of a nerve segment of unit length in normal Ringer. Perineurial hydraulic conductivity (Lp) equals 7.5 x 10(-13) cm3.s-1.dyn-1, a value characteristic of nonleaky epithelia. The perineurium is an elastic tissue with a constant modulus of elasticity equal to 3 x 10(6) dyn/cm2 when not markedly stretched and may limit nerve swelling under pathological conditions of nerve edema.

scholarly journals Mitochondrial Disorders Therapy: The Utility of Melatonin

2010 ◽  
Vol 3 (1) ◽  
pp. 53-65
Author(s):  
Luis C. Lopez ◽  
Dario Acuna-Castroviejo ◽  
Alberto del Pino ◽  
Miguel Tejada ◽  
Germaine Escames
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Action Spectrum ◽  
Cell Physiology ◽  
Stem Cell Proliferation ◽  
Cell Functions ◽  
Mtdna Mutations ◽  
Mitochondrial Homeostasis

Mitochondria play a central role in the cell physiology. It is now recognized that, besides their classic function of energy metabolism, mitochondria are enrolled in multiple cell functions including energy distribution through the cell, energy/heat modulation, reactive oxygen species (ROS) regulation, calcium homeostasis, and apoptosis control. Recently, evidence is accumulating for a direct participation of mitochondria in stem cell proliferation and/or differentiation. All these functions suggest that mutations in either nuclear or mitochondrial DNA may induce serious cell impairments, and there is now evidence of more than 200 mtDNA mutations responsible for human pathologies. Moreover, mitochondria are, simultaneously, the main producer and target of ROS and, thus, multiple mitochondrial diseases are related to ROSinduced mitochondrial injuries. Among these, neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), inflammatory diseases such as sepsis, and aging itself, are caused or accompanied by ROS-induced mitochondrial dysfunctions. With regard to its action spectrum as an antioxidant, melatonin may be regarded as a firstchoice agent for preventing and/or reducing the excess of ROS, thereby maintaining mitochondrial homeostasis. Multiple in vitro and in vivo experiments have shown the protective role of melatonin on mitochondrial physiology, yielding a significant improvement in those diseases in which energy supply to the cell had been compromised. New lines of evidence suggest the participation of mitochondria in stem cell proliferation and differentiation, and preliminary data support the role of melatonin in these processes. This review accounts for the multiple functions of mitochondria and the mechanisms involved in the numerous beneficial effects of melatonin to maintain mitochondrial homeostasis.

scholarly journals The regulatory role of mitochondrial pora and the possibility of its pharmacological modulation

2014 ◽  
Vol 12 (3) ◽  
pp. 13-19 ◽  
Author(s):  
Yelena Vasilyevna Pozhilova ◽  
Vasiliy Egorovich Novikov ◽  
Olga Sergeevna Levchenkova
Keyword(s):  
Tumor Therapy ◽  
Cell Functions ◽  
Pathological Conditions ◽  
Target Action ◽  
Mechanisms Of Adaptation ◽  
Postischemic Period ◽  
Ischemic Diseases ◽  
Pharmacological Regulation ◽  
In Cells

The review is devoted to the role of mitochondrial Ca2+-dependent pore (mPTP) in the regulation of metabolic processes in cells under physiological and pathological conditions. The mechanisms of reperfusion injury in the postischemic period involving mPTP are discussed in the paper. The possibilities of pharmacological regulation of metabolic and functional processes in cells by target action on mPTP work are assessed. This approach allows to regulate key cell functions, stimulating either mechanisms of adaptation and survival in extreme conditions or apoptosis. Pharmacological modulators of the mitochondrial pore as drugs have promising value for treatment of ischemic diseases as well as tumor therapy.

Isolated perfused Ambystoma proximal tubule: hydrodynamics modulates ultrastructure

1987 ◽  
Vol 252 (6) ◽  
pp. F1129-F1147
Author(s):  
S. Tripathi ◽  
E. L. Boulpaep ◽  
A. B. Maunsbach
Keyword(s):  
Hydrostatic Pressure ◽  
Proximal Tubule ◽  
Axial Flow ◽  
Transepithelial Transport ◽  
Ambystoma Tigrinum ◽  
Renal Tubules ◽  
Pressure Gradients ◽  
Pressure Sensing ◽  
Cell Height

A method using a pressure-sensing servo-pipette is described for measuring downstream transepithelial pressure within isolated renal tubules perfused at flow rates designed to keep luminal solution composition constant. The hydrodynamics of in vitro microperfusion of isolated proximal tubules of Ambystoma tigrinum was varied and different states of transepithelial hydrostatic pressure difference, axial tubule flow, and transepithelial transport were correlated with epithelial ultrastructure. Tubules analyzed by ultrastructural morphometry were as follows: unperfused with and without ouabain, perfused single-end cannulated with and without ouabain, and perfused double-end cannulated tubules incubated in substrate Ringer. The results indicate that proximal tubule fine structure is well preserved for more than 3 h in unperfused and perfused tubules. Small transepithelial hydrostatic pressure gradients (less than 162 Pa) increase tubule diameters and decrease cell height without changing volumes of the cells, lateral intercellular spaces (LIS), or the basal extracellular labyrinth (BEL). Pressure gradients of 271 Pa have no further effect on tubule diameters or cell height, but significantly reduce volumes of LIS and BEL. Transport inhibition and axial flow changes have minor structural effects. This study demonstrates a close dependence of tubule ultrastructure on hydrodynamic conditions and provides guidelines for optimizing the latter during perfusion of isolated renal tubules.

scholarly journals Circular RNAs as Novel Regulators of β-Cell Functions under Physiological and Pathological Conditions

2021 ◽  
Vol 22 (4) ◽  
pp. 1503 ◽  
Author(s):  
Flora Brozzi ◽  
Romano Regazzi
Keyword(s):  
Islet Cells ◽  
Circular Rnas ◽  
Diabetic Patients ◽  
Β Cell ◽  
Type 2 Diabetic Patients ◽  
Altered Expression ◽  
Cell Functions ◽  
Pathological Conditions ◽  
Mrna Maturation

Circular RNAs (circRNAs) constitute a large class of non-coding RNAs characterized by a covalently closed circular structure. They originate during mRNA maturation through a modification of the splicing process and, according to the included sequences, are classified as Exonic, Intronic, or Exonic-Intronic. CircRNAs can act by sequestering microRNAs, by regulating the activity of specific proteins, and/or by being translated in functional peptides. There is emerging evidence indicating that dysregulation of circRNA expression is associated with pathological conditions, including cancer, neurological disorders, cardiovascular diseases, and diabetes. The aim of this review is to provide a comprehensive and updated view of the most abundant circRNAs expressed in pancreatic islet cells, some of which originating from key genes controlling the differentiation and the activity of insulin-secreting cells or from diabetes susceptibility genes. We will particularly focus on the role of a group of circRNAs that contribute to the regulation of β-cell functions and that display altered expression in the islets of rodent diabetes models and of type 2 diabetic patients. We will also provide an outlook of the unanswered questions regarding circRNA biology and discuss the potential role of circRNAs as biomarkers for β-cell demise and diabetes development.

scholarly journals Regulation of Nuclear Factor-kappaB Function by O-GlcNAcylation in Inflammation and Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Angela Rose Liu ◽  
Parameswaran Ramakrishnan
Keyword(s):  
Cell Proliferation ◽  
Posttranslational Modifications ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Cancer Cell Proliferation ◽  
The Past ◽  
Pathological Conditions ◽  
Evolutionarily Conserved ◽  
Made In

Nuclear factor-kappaB (NF-κB) is a pleiotropic, evolutionarily conserved transcription factor family that plays a central role in regulating immune responses, inflammation, cell survival, and apoptosis. Great strides have been made in the past three decades to understand the role of NF-κB in physiological and pathological conditions. Carcinogenesis is associated with constitutive activation of NF-κB that promotes tumor cell proliferation, angiogenesis, and apoptosis evasion. NF-κB is ubiquitously expressed, however, its activity is under tight regulation by inhibitors of the pathway and through multiple posttranslational modifications. O-GlcNAcylation is a dynamic posttranslational modification that controls NF-κB-dependent transactivation. O-GlcNAcylation acts as a nutrient-dependent rheostat of cellular signaling. Increased uptake of glucose and glutamine by cancer cells enhances NF-κB O-GlcNAcylation. Growing evidence indicates that O-GlcNAcylation of NF-κB is a key molecular mechanism that regulates cancer cell proliferation, survival and metastasis and acts as link between inflammation and cancer. In this review, we are attempting to summarize the current understanding of the cohesive role of NF-κB O-GlcNAcylation in inflammation and cancer.

scholarly journals Harnessing biomolecular condensates in living cells

2019 ◽  
Vol 166 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Hideki Nakamura ◽  
Robert DeRose ◽  
Takanari Inoue
Keyword(s):  
Living Cells ◽  
Technological Advance ◽  
Liquid Droplets ◽  
Molecular Tools ◽  
Rna Molecules ◽  
Cell Functions ◽  
Pathological Conditions ◽  
A Cell ◽  
Membrane Bound

Abstract As part of the ‘Central Dogma’ of molecular biology, the function of proteins and nucleic acids within a cell is determined by their primary sequence. Recent work, however, has shown that within living cells the role of many proteins and RNA molecules can be influenced by the physical state in which the molecule is found. Within living cells, both protein and RNA molecules are observed to condense into non-membrane-bound yet distinct structures such as liquid droplets, hydrogels and insoluble aggregates. These unique intracellular organizations, collectively termed biomolecular condensates, have been found to be vital in both normal and pathological conditions. Here, we review the latest studies that have developed molecular tools attempting to recreate artificial biomolecular condensates in living cells. We will describe their design principles, implementation and unique characteristics, along with limitations. We will also introduce how these tools can be used to probe and perturb normal and pathological cell functions, which will then be complemented with discussions of remaining areas for technological advance under this exciting theme.

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