Glandular metaplasia of hair follicles and other responses to vitamin A excess in cultures of rodent skin

Development ◽  
1968 ◽  
Vol 19 (2) ◽  
pp. 157-180
Author(s):  
Margaret H. Hardy

The demonstration of mucous metaplasia in chicken embryonic epidermis exposed to an excess of vitamin A (Fell & Mellanby, 1953) stimulated many further investigations (reviewed by Fell, 1964; Fell & Rinaldini, 1965; Dingle & Lucy, 1965), leading to new insights into control of differentiation and function at the cellular level. The object of the present experiments was to study the effects of excess vitamin A on another keratin-producing system, the developing hair follicle, in organotypic cultures. Hairs and their follicles have received little attention from other investigators of vitamin A effects in vitro, although Fell & Mellanby (1953) referred to ‘evidence of an inhibitory effect on hair formation’ in some preliminary experiments with mouse embryonic skin, and New (1963) reported that ‘usually the development of hair follicles was suppressed’ in cultures of embryonic skin from the rat and mouse, both in the presence and absence of excess vitamin A.

2009 ◽  
Vol 102 (5) ◽  
pp. 2581-2593 ◽  
Author(s):  
Tadashi Isa ◽  
William C. Hall

The superior colliculus plays an important role in the translation of sensory signals that encode the location of objects in space into motor signals that encode vectors of the shifts in gaze direction called saccades. Since the late 1990s, our two laboratories have been applying whole cell patch-clamp techniques to in vitro slice preparations of rodent superior colliculus to analyze the structure and function of its circuitry at the cellular level. This review describes the results of these experiments and discusses their contributions to our understanding of the mechanisms responsible for sensorimotor integration in the superior colliculus. The experiments analyze vertical interactions between its superficial visuosensory and intermediate premotor layers and propose how they might contribute to express saccades and to saccadic suppression. They also compare and contrast the circuitry within each of these layers and propose how this circuitry might contribute to the selection of the targets for saccades and to the build-up of the premotor commands that precede saccades. Experiments also explore in vitro the roles of extrinsic inputs to the superior colliculus, including cholinergic inputs from the parabigeminal and parabrachial nuclei and GABAergic inputs from the substantia nigra pars reticulata, in modulating the activity of the collicular circuitry. The results extend and clarify our understanding of the multiple roles the superior colliculus plays in sensorimotor integration.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Shaoxing Wang ◽  
Pedro Jose ◽  
Chunyu Zeng

The dopaminergic and sympathetic systems interact to regulate blood pressure. Our previous studies show the regulation of dopamine receptor on α 1 -adrenergic receptor function. Due to the regulation of renalase on sympathetic tone, we hypothesize that dopamine receptor, especially D 1 -like receptor, might regulate renalase in kidney. The effect of D 1 -like receptor on renalase expression and function was checked in immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). It resulted that D 1 -like receptor agonist, fenoldopam (10 -7 -10 -5 M), increased renalase protein expression and function in WKY RPT cells, in contrast, decreased it in SHR cells. These effects were blocked by D 1 -like receptor antagonist SCH 23390 (10 -6 M). Fenoldopam increased renalase mRNA level in WKY RPT cells, but not in SHR cells. Fenoldopam increased the degradation of renalase protein in both WKY and SHR cells. However, the degradation degree was higher in SHR cells than in WKY cells. The regulation of D 1 -like receptor on renalase was mainly via D 5 receptor, because inhibition of D 5 , not D 1 receptor, by antisense blocked inhibitory effect of D 1 -like receptor on renalase in WKY cells. Moreover, inhibition of PKC, by PKC inhibitor 19-31, blocked the effect of fenoldopam on renalase expression; stimulation of PKC, by PKC agonist (PMA), inhibited renalase expression and function, indicating that PKC is involved in the process. Consistent with the in-vitro study, renalase expression was lower in kidney from SHRs than in WKY rats. It indicated that D 1 -like receptor, via D 5 receptor, regulates renalase expression and function in RPT cells, aberrant regulation of D 5 receptor on renalase might be involved in the pathogenesis of hypertension.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Kyung-Baeg Roh ◽  
Deokhoon Park ◽  
Eunsun Jung

Glucocorticoids are a risk factor for age-induced skin structure and function defects, and the glucocorticoid-activating enzyme, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), represents a promising therapeutic target. Prunella vulgaris L. (PV) is a perennial and an edible herbaceous plant normally cultivated in Asia and Europe. A recent study demonstrated a broad range of biological activities of PV including immune modulatory, antiviral, antiallergic, anti-inflammatory, antioxidant, and antidiabetic. However, little is known about the inhibitory effect of PV on 11β-HSD1. In this study, we investigated the inhibitory effect of Prunella vulgaris L. extract (PVE) and the underlying mechanism of 11β-HSD11 inhibition. Consistent with these results, cortisol levels were also reduced by PVE in vitro. The cortisone-induced translocation of glucocorticoids receptor (GR) was also attenuated. In addition, PVE inhibited a cortisone-mediated decrease in collagen content in skin. Collectively, these results suggest the beneficial effects of PVE in maintaining skin integrity.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Veedamali S. Subramanian ◽  
Trevor Teafatiller ◽  
Anshu Agrawal ◽  
Masashi Kitazawa ◽  
Jonathan S. Marchant

Vitamin C (ascorbic acid: AA) uptake in neurons occurs via the sodium-dependent vitamin C transporter-2 (SVCT2), which is highly expressed in the central nervous system (CNS). During chronic neuroinflammation or infection, CNS levels of lipopolysaccharide (LPS) and LPS-induced tumor necrosis factor-α (TNFα) are increased. Elevated levels of LPS and TNFα have been associated with neurodegenerative diseases together with reduced levels of AA. However, little is known about the impacts of LPS and TNFα on neuronal AA uptake. The objective of this study was to examine the effect of LPS and TNFα on SVCT2 expression and function using in vitro and in vivo approaches. Treatment of SH-SY5Y cells with either LPS or TNFα inhibited AA uptake. This reduced uptake was associated with a significant decrease in SVCT2 protein and mRNA levels. In vivo exposure to LPS or TNFα also decreased SVCT2 protein and mRNA levels in mouse brains. Both LPS and TNFα decreased SLC23A2 promoter activity. Further, the inhibitory effect of LPS on a minimal SLC23A2 promoter was attenuated when either the binding site for the transcription factor Sp1 was mutated or cells were treated with the NF-κB inhibitor, celastrol. We conclude that inflammatory signals suppress AA uptake by impairing SLC23A2 transcription through opposing regulation of Sp1 and NF-κB factors.


In earlier experiments, Fell & Mellanby (1953) showed that the simple, two-layered epidermis of the 7-day embryonic chick underwent mucous metaplasia when grown in medium containing excess vitamin A. The present investigation was undertaken to see whether epidermis at more advanced stages of development would undergo a similar transformation in vitro under the influence of vitamin A. Skin from the shank and foot of 13-, 14- and 18-day chick embryos was grown on rayon acetate cloth by Shaffer’s modification of the watch-glass method, in medium (cock plasma and embryo extract) to which natural or synthetic vitamin A alcohol had been added. For purposes of comparison, one experiment was made with skin from the trunk and limbs of 7-day embryos. A dose of 1500 i. u. vitamin A /100 ml. of culture medium completely inhibited keratinization in all the + A explants, whatever the age of the embryo from which they were obtained. This concentration induced mucous metaplasia in all the explants from 7- and 13-day chicks, and in a minority of those from 18-day embryos. In the 13- and 18-day explants, the outer strata of epidermal cells degenerated and were sloughed, and the secretory epithelium was formed from the deepest and least differentiated layers. The dermis also was affected by the vitamin. When the explants were transferred from + A to normal medium, mucin secretion at first increased, often becoming astonishingly copious; later the mucous tissue was shed and the deeper cells regenerated a squamous, keratinizing epidermis. In all the controls grown on normal medium, the epidermis retained its squamous structure and formed increasing amounts of keratin, except at the margin of the 7- and 13-day cultures; here the newly formed epithelium, which had spread beyond or below the dermis, often failed to cornify and in one 7-day control, which elsewhere was heavily keratinized, it even developed some secretory cells. This peripheral effect is thought to be due to the close and prolonged contact of the outwandering epithelium with the fairly high level of vitamin A normally present in fowl blood plasma. The concentrations of vitamin A used in the present experiments were much less than those that can be produced in the blood of fowls fed on a high vitamin A diet. The vitamin A in the culture medium, however, may be much more readily available to the epidermis than the same concentrations of vitamin in the blood stream of a hypervitaminotic bird. It is also probable that the vitamin is in a more active state in the culture medium than it is in vivo (cf. Fell & Mellanby 1952).


2019 ◽  
Vol 20 (8) ◽  
pp. 1966 ◽  
Author(s):  
Yujuan Zhang ◽  
Li Guo ◽  
Jinhu Huang ◽  
Yong Sun ◽  
Fang He ◽  
...  

Overcoming P-glycoprotein (P-gp) efflux is a strategy to improve the absorption and pharmacokinetics of its substrate drugs. Berberine inhibits P-gp and thereby increases the bioavailability of the P-gp substrate digoxin in rodents. However, the effects of berberine on P-gp in chickens are still unclear. Here, we studied the role of berberine in modulating broilers P-gp expression and function through both in situ and in vitro models. In addition, molecular docking was applied to analyze the interactions of berberine with P-gp as well as with chicken xenobiotic receptor (CXR). The results showed that the mRNA expression levels of chicken P-gp and CXR decreased in the ileum following exposure to berberine. The absorption rate constant of rhodamine 123 increased after berberine treatment, as detected using an in situ single-pass intestinal perfusion model. Efflux ratios of P-gp substrates (tilmicosin, ciprofloxacin, clindamycin, ampicillin, and enrofloxacin) decreased and the apparent permeability coefficients increased after co-incubation with berberine in MDCK-chAbcb1 cell models. Bidirectional assay results showed that berberine could be transported by chicken P-gp with a transport ratio of 4.20, and this was attenuated by verapamil (an inhibitor of P-gp), which resulted in a ratio of 1.13. Molecular docking revealed that berberine could form favorable interactions with the binding pockets of both CXR and P-gp, with docking scores of −7.8 and −9.5 kcal/mol, respectively. These results indicate that berberine is a substrate of chicken P-gp and down-regulates P-gp expression in chicken tissues, thereby increasing the absorption of P-gp substrates. Our findings suggest that berberine increases the bioavailability of other drugs and that drug-drug interactions should be considered when it is co-administered with other P-gp substrates with narrow therapeutic windows.


Author(s):  
Singaravelu Anand ◽  
Munichetty Arasakumari ◽  
Panneervelu Prabu ◽  
Arul Joseph Amalraj

<p><strong>Objective: </strong>The objective of the present study was to determine the cellular level effect on glucose uptake and aldose reductase inhibitory activity of different extracts of traditional medicinal plant <em>Psidium guajava</em>.</p><p><strong>Methods: </strong><em>Psidium guajava</em> was selected and subjected for successive extraction from non-polar to polar solvents and subjected to glucose uptake and aldose reductase inhibition assay.</p><p><strong>Results: </strong>Based on the results <em>Psidium guajava</em><em> </em>methanolic extract (PGME) showed an enhancement in the glucose uptake and also up-regulates the gene and protein level expression of IRβ, IRS-1, PI3K and GLUT4. Wortmannin, a specific PI3K inhibitor confirms that the active PGME recruits glucose uptake through a PI3K dependent pathway. In the assay of aldose reductase inhibitory activity, the results suggested that PGME possesses a significant inhibitory effect.</p><p><strong>Conclusion: </strong>The result obtained in the present study focuses on the anti-diabetic effect of PGME by studying cellular level glucose uptake in L6 myotubes and aldose reductase inhibitory activity.<strong></strong></p>


2021 ◽  
Vol 22 (15) ◽  
pp. 8235
Author(s):  
Gink N. Yang ◽  
Parinaz Ahangar ◽  
Xanthe L. Strudwick ◽  
Zlatko Kopecki ◽  
Allison J. Cowin

Epidermal progenitor cells divide symmetrically and asymmetrically to form stratified epidermis and hair follicles during late embryonic development. Flightless I (Flii), an actin remodelling protein, is implicated in Wnt/β-cat and integrin signalling pathways that govern cell division. This study investigated the effect of altering Flii on the divisional orientation of epidermal progenitor cells (EpSCs) in the basal layer during late murine embryonic development and early adolescence. The effect of altering Flii expression on asymmetric vs. symmetric division was assessed in vitro in adult human primary keratinocytes and in vivo at late embryonic development stages (E16, E17 and E19) as well as adolescence (P21 day-old) in mice with altered Flii expression (Flii knockdown: Flii+/−, wild type: WT, transgenic Flii overexpressing: FliiTg/Tg) using Western blot and immunohistochemistry. Flii+/− embryonic skin showed increased asymmetrical cell division of EpSCs with an increase in epidermal stratification and elevated talin, activated-Itgb1 and Par3 expression. FliiTg/Tg led to increased symmetrical cell division of EpSCs with increased cell proliferation rate, an elevated epidermal SOX9, Flap1 and β-cat expression, a thinner epidermis, but increased hair follicle number and depth. Flii promotes symmetric division of epidermal progenitor cells during murine embryonic development.


Materials ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 1970
Author(s):  
Giorgia Fedele ◽  
Sara Castiglioni ◽  
Jeanette A. Maier ◽  
Laura Locatelli

Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mengbo Zhu ◽  
Wenbin Xu ◽  
Jiuzhou Jiang ◽  
Yining Wang ◽  
Yanjing Guo ◽  
...  

Osteoclasts (OCs) play an important role in osteoporosis, a disease that is mainly characterized by bone loss. In our research, we aimed to identify novel approach for regulating osteoclastogenesis and thereby treating osteoporosis. Previous studies have set a precedent for screening traditional Chinese herbal extracts for effective inhibitors. Peiminine is an alkaloid extracted from the bulb of Fritillaria thunbergii Miq that reportedly has anticancer and anti-inflammatory effects. Thus, the potential inhibitory effect of peiminine on OC differentiation was investigated via a series of experiments. According to the results, peiminine downregulated the levels of specific genes and proteins in vitro and consequently suppressed OC differentiation and function. Based on these findings, we further investigated the underlying molecular mechanisms and identified the NF-κB and ERK1/2 signaling pathways as potential targets of peiminine. In vivo, peiminine alleviated bone loss in an ovariectomized mouse model.


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