scholarly journals The Complexities of Organ Crosstalk in Phosphate Homeostasis: Time to Put Phosphate Sensing Back in the Limelight

2021 ◽  
Vol 22 (11) ◽  
pp. 5701
Author(s):  
Lucile Figueres ◽  
Sarah Beck-Cormier ◽  
Laurent Beck ◽  
Joanne Marks
Keyword(s):  
Molecular Mechanisms ◽  
Dominant Role ◽  
Fibroblast Growth Factor 23 ◽  
Hormone Secretion ◽  
Phosphate Transport ◽  
Phosphate Homeostasis ◽  
Cellular Mechanisms ◽  
Exact Function ◽  
Phosphate Sensing ◽  
Significant Research

Phosphate homeostasis is essential for health and is achieved via interaction between the bone, kidney, small intestine, and parathyroid glands and via intricate processes involving phosphate transporters, phosphate sensors, and circulating hormones. Numerous genetic and acquired disorders are associated with disruption in these processes and can lead to significant morbidity and mortality. The role of the kidney in phosphate homeostasis is well known, although it is recognized that the cellular mechanisms in murine models and humans are different. Intestinal phosphate transport also appears to differ in humans and rodents, with recent studies demonstrating a dominant role for the paracellular pathway. The existence of phosphate sensing has been acknowledged for decades; however, the underlying molecular mechanisms are poorly understood. At least three phosphate sensors have emerged. PiT2 and FGFR1c both act as phosphate sensors controlling Fibroblast Growth Factor 23 secretion in bone, whereas the calcium-sensing receptor controls parathyroid hormone secretion in response to extracellular phosphate. All three of the proposed sensors are expressed in the kidney and intestine but their exact function in these organs is unknown. Understanding organ interactions and the mechanisms involved in phosphate sensing requires significant research to develop novel approaches for the treatment of phosphate homeostasis disorders.

Effect of cortisol on neurophysin I/oxytocin and peptidyl glycine-α-amidating mono-oxygenase mRNA expression in bovine luteal and granulosa cells

2013 ◽  
Vol 16 (2) ◽  
pp. 231-239
Author(s):  
A. Ziolkowska ◽  
J. Mlynarczuk ◽  
J. Kotwica
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Oestrous Cycle ◽  
Luteal Cells ◽  
Ru 486 ◽  
Ovarian Cells ◽  
Key Genes ◽  
Ovary Function

Abstract Cortisol stimulates the synthesis and secretion of oxytocin (OT) from bovine granulosa and luteal cells, but the molecular mechanisms of cortisol action remain unknown. In this study, granulosa cells or luteal cells from days 1-5 and 11-15 of the oestrous cycle were incubated for 4 or 8 h with cortisol (1x10-5, 1x10-7 M). After testing cell viability and hormone secretion (OT, progesterone, estradiol), we studied the effect of cortisol on mRNA expression for precursor of OT (NP-I/OT) and peptidyl glycine-α-amidating mono-oxygenase (PGA). The influence of RU 486 (1x10-5 M), a progesterone receptor blocker and inhibitor of the glucocorticosteroid receptor (GR), on the expression for both genes was tested. Cortisol increased the mRNA expression for NP-I/OT and PGA in granulosa cells and stimulated the expression for NP-I/OT mRNA in luteal cells obtained from days 1-5 and days 11-15 of the oestrous cycle. Expression for PGA mRNA was increased only in luteal cells from days 11-15 of the oestrous cycle. In addition, RU 486 blocked the cortisol-stimulated mRNA expression for NP-I/OT and PGA in both types of cells. These data suggest that cortisol affects OT synthesis and secretion in bovine ovarian cells, by acting on the expression of key genes, that may impair ovary function.

Natural Products for Regulating Macrophages M2 Polarization

2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Research Progress ◽  
Cellular Mechanisms ◽  
Pharmacological Activities ◽  
Current Review ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
Herbal Plants

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

scholarly journals Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1134
Author(s):  
Hao-Qi Wang ◽  
Wei-Di Zhang ◽  
Bao Yuan ◽  
Jia-Bao Zhang
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Β Subunit ◽  
Glycoprotein Hormone ◽  
Livestock Breeding ◽  
Biological Specificity ◽  
Therapeutic Development ◽  
Stimulating Hormone

Mammalian reproduction is mainly driven and regulated by the hypothalamic-pituitary-gonadal (HPG) axis. Follicle-stimulating hormone (FSH), which is synthesized and secreted by the anterior pituitary gland, is a key regulator that ultimately affects animal fertility. As a dimeric glycoprotein hormone, the biological specificity of FSH is mainly determined by the β subunit. As research techniques are being continuously innovated, studies are exploring the underlying molecular mechanism regulating the secretion of mammalian FSH. This article will review the current knowledge on the molecular mechanisms and signaling pathways systematically regulating FSH synthesis and will present the latest hypothesis about the nuclear cross-talk among the various endocrine-induced pathways for transcriptional regulation of the FSH β subunit. This article will provide novel ideas and potential targets for the improved use of FSH in livestock breeding and therapeutic development.

Fibroblast growth factor 23 and its role in phosphate homeostasis in growing children compared to adults

2020 ◽  
Vol 33 (8) ◽  
pp. 1065-1071
Author(s):  
Marjan Jeddi ◽  
Maryam Heidari ◽  
Neda Hatami ◽  
Gholam Hossein Ranjbar Omrani
Keyword(s):  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Fibroblast Growth Factor 23 ◽  
Fractional Excretion ◽  
Cross Sectional Study ◽  
Fibroblast Growth ◽  
Sectional Study ◽  
Phosphate Homeostasis ◽  
Cross Sectional ◽  
Fractional Excretion Of Phosphate

AbstractObjectivesPhosphate is essential for skeletal mineralization, which is regulated by parathyroid hormone, calcitriol and fibroblast growth factor 23 (FGF23). Serum phosphate is physiologically higher in younger children, but factors that contribute to this physiological state are poorly understood. This study aimed to evaluate phosphate and its regulators in children compared with adults.Materials and methodsThe participants were children aged 3–11 years and adults older than 20 years of age. Biochemical parameters including calcium, phosphorus, alkaline phosphatase, FGF23, and vitamin D were measured. Fractional excretion of phosphate was calculated, using serum and urine phosphate and creatinine.ResultsThis cross-sectional study was conducted on 45 children (mean age: 9.0 ± 2.1) and 44 adults (mean age: 38.9 ± 11.1). The children had higher serum calcium, phosphate, alkaline phosphatase, and FGF23 (p < 0.001), but fractional excretion of phosphate was greater in adults (14.1 ± 5.7, 11.4 ± 4.4, p = 0.019, 95% confidence interval [CI]: −0.7 to −0.2). Of all individuals, 61.8% had vitamin D deficiency. By multiple regression analysis, entering age, calcium, phosphate, and vitamin D level, the only independent predictor of FGF23 was 1, 25 dihydroxy-vitamin D3 (β: 0.78, p < 0.001, 95% CI: 0.5–1.1, R2: 0.59 for children, and β: 0.59, p < 0.001, 95% CI: 0.5–1.4, R2: 0.45 for adults).ConclusionAs far as we know, there is little information regarding the role of FGF23 in physiologic state. In this cross-sectional study no association was found between FGF23 and urinary phosphate excretion in growing children. Further studies with more detail are essential to evaluate phosphate homeostasis during childhood.

scholarly journals Neuropathology of the Brainstem to Mechanistically Understand and to Treat Alzheimer’s Disease

2021 ◽  
Vol 10 (8) ◽  
pp. 1555
Author(s):  
Ágoston Patthy ◽  
János Murai ◽  
János Hanics ◽  
Anna Pintér ◽  
Péter Zahola ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Brain Structures ◽  
Specific Information ◽  
Cellular Mechanisms ◽  
Monoaminergic System ◽  
Monoaminergic Neurons

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder as yet without effective therapy. Symptoms of this disorder typically reflect cortical malfunction with local neurohistopathology, which biased investigators to search for focal triggers and molecular mechanisms. Cortex, however, receives massive afferents from caudal brain structures, which do not only convey specific information but powerfully tune ensemble activity. Moreover, there is evidence that the start of AD is subcortical. The brainstem harbors monoamine systems, which establish a dense innervation in both allo- and neocortex. Monoaminergic synapses can co-release neuropeptides either by precisely terminating on cortical neurons or, when being “en passant”, can instigate local volume transmission. Especially due to its early damage, malfunction of the ascending monoaminergic system emerges as an early sign and possible trigger of AD. This review summarizes the involvement and cascaded impairment of brainstem monoaminergic neurons in AD and discusses cellular mechanisms that lead to their dysfunction. We highlight the significance and therapeutic challenges of transmitter co-release in ascending activating system, describe the role and changes of local connections and distant afferents of brainstem nuclei in AD, and summon the rapidly increasing diagnostic window during the last few years.

G-protein-coupled receptors signalling at the cell nucleus: an emerging paradigmThis paper is one of a selection of papers published in this Special Issue, entitled The Nucleus: A Cell Within A Cell.

2006 ◽  
Vol 84 (3-4) ◽  
pp. 287-297 ◽  
Author(s):  
Fernand Gobeil ◽  
Audrey Fortier ◽  
Tang Zhu ◽  
Michela Bossolasco ◽  
Martin Leduc ◽  
...  
Keyword(s):  
G Protein ◽  
Cell Nucleus ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Cell Metabolism ◽  
Hormone Secretion ◽  
G Protein Coupled Receptors ◽  
A Cell ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) comprise a wide family of monomeric heptahelical glycoproteins that recognize a broad array of extracellular mediators including cationic amines, lipids, peptides, proteins, and sensory agents. Thus far, much attention has been given towards the comprehension of intracellular signaling mechanisms activated by cell membrane GPCRs, which convert extracellular hormonal stimuli into acute, non-genomic (e.g., hormone secretion, muscle contraction, and cell metabolism) and delayed, genomic biological responses (e.g., cell division, proliferation, and apoptosis). However, with respect to the latter response, there is compelling evidence for a novel intracrine mode of genomic regulation by GPCRs that implies either the endocytosis and nuclear translocation of peripheral-liganded GPCR and (or) the activation of nuclearly located GPCR by endogenously produced, nonsecreted ligands. A noteworthy example of the last scenario is given by heptahelical receptors that are activated by bioactive lipoids (e.g., PGE2 and PAF), many of which may be formed from bilayer membranes including those of the nucleus. The experimental evidence for the nuclear localization and signalling of GPCRs will be reviewed. We will also discuss possible molecular mechanisms responsible for the atypical compartmentalization of GPCRs at the cell nucleus, along with their role in gene expression.

scholarly journals Hypoxia-Induced Epithelial-Mesenchymal Transition Is Involved in Bleomycin-Induced Lung Fibrosis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Liang Guo ◽  
Jun-mei Xu ◽  
Lei Liu ◽  
Su-mei Liu ◽  
Rong Zhu
Keyword(s):  
P38 Mapk ◽  
Lung Fibrosis ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Severe Disease ◽  
Progressive Increase ◽  
Lung Epithelial Cells ◽  
Cellular Mechanisms ◽  
Mesenchymal Transition ◽  
Protein Levels

Pulmonary fibrosis is a severe disease that contributes to the morbidity and mortality of a number of lung diseases. However, the molecular and cellular mechanisms leading to lung fibrosis are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in bleomycin-induced lung fibrosis. The bleomycin-induced fibrosis animal model was established by intratracheal injection of a single dose of bleomycin. Protein expression was measured by Western blot, immunohistochemistry, and immunofluorescence. Typical lesions of lung fibrosis were observed 1 week after bleomycin injection. A progressive increase in MMP-2, S100A4,α-SMA, HIF-1α, ZEB1, CD44, phospho-p44/42 (p-p44/42), and phospho-p38 MAPK (p-p38) protein levels as well as activation of EMT was observed in the lung tissues of bleomycin mice. Hypoxia increased HIF-1αand ZEB1 expression and activated EMT in H358 cells. Also, continuous incubation of cells under mild hypoxic conditions increased CD44, p-p44/42, and p-p38 protein levels in H358 cells, which correlated with the increase in S100A4 expression. In conclusion, bleomycin induces progressive lung fibrosis, which may be associated with activation of EMT. The fibrosis-induced hypoxia may further activate EMT in distal alveoli through a hypoxia-HIF-1α-ZEB1 pathway and promote the differentiation of lung epithelial cells into fibroblasts through phosphorylation of p38 MAPK and Erk1/2 proteins.

Postischemic Revascularization: From Cellular and Molecular Mechanisms to Clinical Applications

2013 ◽  
Vol 93 (4) ◽  
pp. 1743-1802 ◽  
Author(s):  
Jean-Sébastien Silvestre ◽  
David M. Smadja ◽  
Bernard I. Lévy
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Vascular Wall ◽  
Arterial Disease ◽  
Cellular Mechanisms ◽  
Collateral Growth ◽  
Vessel Growth ◽  
Ischemic Diseases

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

scholarly journals Identification of Differentially Expressed Genes in Porcine Ovaries at Proestrus and Estrus Stages Using RNA-Seq Technique

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Songbai Yang ◽  
Xiaolong Zhou ◽  
Yue Pei ◽  
Han Wang ◽  
Ke He ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Hormone Secretion ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
The Novel ◽  
Kegg Pathways ◽  
Go Enrichment ◽  
Single Organism

Estrus is an important factor for the fecundity of sows, and it is involved in ovulation and hormone secretion in ovaries. To better understand the molecular mechanisms of porcine estrus, the expression patterns of ovarian mRNA at proestrus and estrus stages were analyzed using RNA sequencing technology. A total of 2,167 differentially expressed genes (DEGs) were identified (P≤0.05, log2  Ratio≥1), of which 784 were upregulated and 1,383 were downregulated in the estrus compared with the proestrus group. Gene Ontology (GO) enrichment indicated that these DEGs were mainly involved in the cellular process, single-organism process, cell and cell part, and binding and metabolic process. In addition, a pathway analysis showed that these DEGs were significantly enriched in 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including cell adhesion molecules, ECM-receptor interaction, and cytokine-cytokine receptor interaction. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) confirmed the differential expression of 10 selected DEGs. Many of the novel candidate genes identified in this study will be valuable for understanding the molecular mechanisms of the sow estrous cycle.

Age-associated features of the expression level of apoptosis markers in cardiomyocytes of patients with dilated cardiomyopathy

2022 ◽  
pp. 885-890
Author(s):  
К.П. Кравченко ◽  
К. Л. Козлов ◽  
А.О. Дробинцева ◽  
Д.С. Медведев ◽  
В.О. Полякова
Keyword(s):  
Cell Death ◽  
Dilated Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Confocal Laser ◽  
Control Group ◽  
Cellular Mechanisms ◽  
Apoptosis Pathway ◽  
Bax Protein

Для понимания патогенеза дилатационной кардиомиопатии (ДКМП) необходимо установить молекулярно-клеточные механизмы старения миокарда, в том числе связанные с программируемой клеточной гибелью, молекулярные механизмы которого практически не изучены. Цель работы - изучение маркеров апоптоза в кардиомиоцитах у пациентов с ДКМП in vitro. В работе использовали метод первичных диссоциированных клеточных культур и метод иммунофлюоресцентной конфокальной лазерной микроскопии. Для моделирования клеточного старения использовали клетки 3-го и 14-го пассажей, соответствующие «молодым» и «старым» культурам. На молекулярном уровне старение клеток кардиомиоцитов сопровождалось повышением экспрессии р16 в 2 раза по сравнению с «молодыми культурами» как в контрольной, так и в группе с ДКМП. Также установлено, что экспрессия р16 в культурах, взятых от пациентов с патологией, была в 2 раза выше, чем в аналогичных культурах от здоровых пациентов. Экспрессия р21 была повышена в группе с ДКМП по сравнению с контрольной группой, однако при старении культуры экспрессия p21 не изменялась, оставаясь на высоком уровне. Наиболее значимые различия были получены при сравнении экспрессии Bax в культуре клеток кардиомиоцитов из группы с ДКМП в «молодой» культуре с нормой - в 3,2 раза. Старение клеток миокарда на молекулярном уровне проявлялось в повышении экспрессии белка Baх, именно он является запускающим механизмом митохондриального пути апоптоза. Возможно, этот путь клеточной гибели является превалирующем при ДКМП. To understand the pathogenesis of dilated cardiomyopathy (DCMP), it is necessary to establish the molecular-cellular mechanisms of myocardial aging, including those associated with programmed cell death, the molecular mechanisms of which have not been practically studied. The aim of this work is to study markers of apoptosis in cardiomyocytes of patients with DCMP in vitro. We used the method of primary dissociated cell cultures and the method of immunofluorescence confocal laser microscopy. Cells of the 3 and 14 passages, corresponding to «young» and «old» cultures, were used to simulate cellular senescence. Results. At the molecular level, aging of cardiomyocyte cells was accompanied by a twofold increase in the expression of p16 compared to «young cultures» both in the control group and in the group with DCMP. It was also found that the expression of p16 in cultures taken from patients with pathology was 2 times higher than in similar cultures from healthy patients. The expression of p21 was increased in the group with DCMP compared to the control; however, with aging of the culture, the expression of p21 did not change, remaining at a significant level. The most significant differences were obtained when comparing the expression of Bax in the cell culture of cardiomyocytes from the group with DCMP in a «young» culture compared with the norm, 3,2 times. Aging of myocardial cells at the molecular level was manifested in an increase in the expression of the Bax protein, which is the triggering mechanism of the mitochondrial apoptosis pathway. It is possible that this pathway of cell death is prevalent in DCMP.

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