DCN
Decorin precursor (Bone proteoglycan II) (PG-S2) (PG40) [SLRR1B]
PublicationsПравить
Aging impairs the IGF-I signaling of bone marrow mesenchymal stem cells (bmMSCs), but the mechanism is unclear. Here, we found that the ability to auto-phosphorylate IGF-I receptor (IGF-IR) in response to IGF-I was decreased in the bmMSCs of aged donors. Conversely, data showed that decorin (DCN) expression was prominently increased in aged bmMSCs, and that under IGF-I treatment, DCN knockdown in serum-starved aged bmMSCs potentiated their mitogenic activity and IGF-IR auto-phosphorylation, whereas DCN overexpression in serum-starved adult bmMSCs decreased both activities. Co-immunoprecipitation assays suggested that IGF-I and DCN bound to IGF-IR in a competitive manner. Online MethPrimer predicted 4 CpG islands (CGIs) in the introns of [i]DCN[/i] gene. RT-qPCR and bisulfite sequencing showed that dimethyloxalylglycine, an inhibitor of DNA demethylation, increased [i]DCN[/i] mRNA expression and CGI-I methylation in adult bmMSCs, whereas 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, decreased [i]DCN[/i] mRNA expression and CGI-I methylation in aged bmMSCs, and ultimately enhanced the proliferation of serum-starved aged bmMSCs under IGF-I stimulation. Thus, IGF-IR could be the prime target of aging in down-regulating the IGF-I signaling of bmMSCs, where DCN could be a critical mediator.
Keywords
- IGF-I
- aging
- bone marrow mesenchymal stem cell
- osteoporosis
- small leucine-rich proteoglycan
The cochlear nucleus (CN) transforms the spike trains of spiral ganglion cells into a set of sensory representations that are essential for auditory discriminations and perception. These transformations require the coordinated activity of different classes of neurons that are embryologically derived from distinct sets of precursors. Decades of investigation have shown that the neurons of the CN are differentiated by their morphology, neurotransmitter receptors, ion channel expression and intrinsic excitability. In the present study we have used linear discriminant analysis (LDA) to perform an unbiased analysis of measures of the responses of CN neurons to current injections to objectively categorize cells on the basis of both morphology and physiology. Recordings were made from cells in brain slices from CBA/CaJ mice and a transgenic mouse line, NF107, crossed against the Ai32 line. For each cell, responses to current injections were analyzed for spike rate, spike shape, input resistance, resting membrane potential, membrane time constant, hyperpolarization-activated sag and time constant. Cells were filled with dye for morphological classification, and visually classified according to published accounts. The different morphological classes of cells were separated with the LDA. Ventral cochlear nucleus (VCN) bushy cells, planar multipolar (T-stellate) cells, and radiate multipolar (D-stellate) cells were in separate clusters and separate from all of the neurons from the dorsal cochlear nucleus (DCN). Within the DCN, the pyramidal cells and tuberculoventral cells were largely separated from a distinct cluster of cartwheel cells. principal axes, whereas VCN cells were in 3 clouds approximately orthogonal to this plane. VCN neurons from the two mouse strains overlapped but were slightly separated, indicating either a strain dependence or differences in slice preparation methods. We conclude that cochlear nucleus neurons can be objectively distinguished based on their intrinsic electrical properties, but such distinctions are still best aided by morphological identification.
MeSH Terms
- Action Potentials
- Aging
- Animals
- Cell Shape
- Cochlear Nucleus
- Discriminant Analysis
- Mice, Inbred CBA
- Neurons
- Principal Component Analysis
To investigate the effect of a single and 15 units of high-intensity circuit training (HICT) programme on glucose metabolism, myokines' response and selected genes' expression in women. Thirty-three, non-active women (mean age: 38 ± 12) were split into a HICT (n = 20) or a control group (CON, n = 13). The training protocol included three circuits of nine exercises with own body weight as a workload performed 3 times a week for five weeks. The CON group performed HICT twice. Blood samples were taken before, 1 h and 24 h after the first and last unit to determine IGF-1, myostatin, irisin, decorin, HSP27, interleukin-15 concentrations using the ELISA immunoenzymatic method. To evaluate HSPB1, TNF-α and DCN mRNA, real-time PCR was used. Pre- and post-intervention, the oral glucose test and body composition assessment were completed. The following parameters tended to decrease after the 5-week HICT program: insulin and HOMA-IR Training diminished insulin/IGF-1 ratio (51% CI: -63% to -34%) and induced the drop of myostatin concentration but significantly only among middle-aged women and at baseline insulin resistance. Obtained data revealed that HICT improved an insulin sensitivity and diminished myostatin concentration among older, insulin-resistant women with lower baseline physical capacity.
MeSH Terms
- Adult
- Age Factors
- Aging
- Blood Glucose
- Body Composition
- Circuit-Based Exercise
- Decorin
- Energy Metabolism
- Exercise
- Exercise Therapy
- Exercise Tolerance
- Female
- Gene Expression Regulation
- Heat-Shock Proteins
- Humans
- Insulin
- Insulin Resistance
- Insulin-Like Growth Factor I
- Middle Aged
- Myostatin
- Physical Fitness
- Resistance Training
- Young Adult
Keywords
- Decorin
- Heat shock protein
- Insulin growth factors
- Insulin resistance
- Oral glucose tolerance test
Intervertebral disc degeneration (IDD) is a major contributor to back, neck, and radicular pain, and the treatment of IDD is costly and relatively ineffective. Dysregulation of microRNAs (miRNAs) has been reported to be involved in IDD. The purpose of our study is to illustrate the potential that miR-143-5p targeting eEF2 gene mediates IDD. Following the establishment of the IDD rat models, expression of miR-143-5p, eEF2, Bcl-2, Bax, AMPK, mTOR, cyclinD, COL2, ACAN, and DCN was detected. The NP cells isolated from degenerative intervertebral disc (IVD) were introduced with a series of mimic, inhibitor, or AICAR to explore the functional role of miR-143-5p in IDD and to characterize the relationship between miR-143-5p and eEF2. Cell viability, cell cycle, apoptosis, and senescence were also evaluated. A reduction in eEF2, an increase in miR-143-5p, and activation of the AMPK signaling pathway were observed in degenerative IVD. Moreover, increased senescent NP cells were observed in degenerative IVD. eEF2 was confirmed as a target gene of miR-143-5p. miR-143-5p was found to activate the AMPK signaling pathway. The restoration of miR-143-5p or the activation of AMPK signaling pathway decreased COL2, ACAN, and DCN expression, coupled with the inhibition of NP cell proliferation and differentiation, and promotion of NP apoptosis and senescence. On the contrary, the inhibition of miR-143-5p led to the reversed results. The results demonstrated that the inhibition of miR-143-5p may act as a suppressor for the progression of IDD.
MeSH Terms
- AMP-Activated Protein Kinases
- Animals
- Cells, Cultured
- Elongation Factor 2 Kinase
- Intervertebral Disc Degeneration
- Male
- MicroRNAs
- Rats
- Rats, Inbred Lew
- Signal Transduction
Keywords
- AMPK signaling pathway
- Apoptosis
- Differentiation
- EEF2
- MicroRNA-143-5p
- Nucleus pulposus cells
- Senescence
The main objective of the study was to assess the effect of age on target tissue total gadolinium (Gd) retention after repeated administration of gadodiamide (linear) or gadoterate (macrocyclic) Gd-based contrast agent (GBCA) in rats. The secondary objective was to assess the potential developmental and long-term consequences of GBCA administration during neonatal and juvenile periods. A total of 20 equivalent human clinical doses (cumulated dose, 12 mmol Gd/kg) of either gadoterate or gadodiamide were administered concurrently by the intravenous route to healthy adult and juvenile rats. Saline was administered to juvenile rats forming the control group. In juvenile rats, the doses were administered from postnatal day 12, that is, once the blood-brain barrier is functional as in humans after birth. The tests were conducted on 5 juvenile rats per sex and per group and on 3 adult animals per sex and per group. T1-weighted magnetic resonance imaging of the cerebellum was performed at 4.7 T during both the treatment and treatment-free periods. Behavioral tests were performed in juvenile rats. Rats were euthanatized at 11 to 12 weeks (ie, approximately 3 months) after the last administration. Total Gd concentrations were measured in plasma, skin, bone, and brain by inductively coupled plasma mass spectrometry. Cerebellum samples from the juvenile rats were characterized by histopathological examination (including immunohistochemistry for glial fibrillary acidic protein or GFAP, and CD68). Lipofuscin pigments were also studied by fluorescence microscopy. All tests were performed blindly on randomized animals. Transient skin lesions were observed in juvenile rats (5/5 females and 2/4 males) and not in adult rats having received gadodiamide. Persisting (up to completion of the study) T1 hyperintensity in the deep cerebellar nuclei (DCNs) was observed only in gadodiamide-treated rats. Quantitatively, a slightly higher progressive increase in the DCN/brain stem ratio was observed in adult rats compared with juvenile rats, whereas no difference was noted visually. In all tissues, total Gd concentrations were higher (10- to 30-fold higher) in the gadodiamide-treated groups than in the gadoterate groups. No age-related differences were observed except in bone marrow where total Gd concentrations in gadodiamide-treated juvenile rats were higher than those measured in adults and similar to those measured in cortical bone tissue. No significant treatment-related effects were observed in histopathological findings or in development, behavior, and biochemistry parameters. However, in the elevated plus maze test, a trend toward an anxiogenic effect was observed in the gadodiamide group compared with other groups (nonsignificant). Moreover, in the balance beam test, a high number of trials were excluded in the gadodiamide group because rats (mainly males) did not completely cross the beam, which may also reflect an anxiogenic effect. No T1 hyperintensity was observed in the DCN after administration of the macrocyclic GBCA gadoterate regardless of age as opposed to administration of the linear GBCA gadodiamide. Repeated administration of gadodiamide in neonatal and juvenile rats resulted in similar total Gd retention in the skin, brain, and bone to that in adult rats with sex having no effect, whereas Gd distribution in bone marrow was influenced by age. Further studies are required to assess the form of the retained Gd and to investigate the potential risks associated with Gd retention in bone marrow in juvenile animals treated with gadodiamide. Regardless of age, total Gd concentration in the brain and bone was 10- to 30-fold higher after administration of gadodiamide compared with gadoterate.
MeSH Terms
- Age Factors
- Aging
- Animals
- Bone and Bones
- Brain
- Contrast Media
- Disease Models, Animal
- Female
- Gadolinium DTPA
- Heterocyclic Compounds
- Male
- Microscopy, Fluorescence
- Organometallic Compounds
- Rats
- Rats, Sprague-Dawley
- Spectrophotometry, Atomic
Hair follicle stem cells (HFSC) are localized in the bulge region of the hair follicle and play a role in producing hair. Recently, it has been shown that the number of HFSC decreases with age, which is thought to be a cause of senile alopecia. Therefore, maintaining HFSC may be key for the prevention of age-related hair loss, but the regulatory mechanisms of HFSC and the effects of aging on them are largely unknown. In general, stem cells are known to require regulatory factors in the pericellular microenvironment, termed the stem cell niche, to maintain their cell function. In this study, we focused on the extracellular matrix proteoglycan decorin (DCN) as a candidate factor for maintaining the human HFSC niche. Gene expression analysis showed that DCN was highly expressed in the bulge region. We observed decreases in DCN expression as well as the number of KRT15-positive HFSC with age. In vitro experiments with human plucked hair-derived HFSC revealed that HFSC lost their undifferentiated state with increasing passages, and prior to this change a decrease in DCN expression was observed. Furthermore, knockdown of DCN promoted HFSC differentiation. In contrast, when HFSC were cultured on DCN-coated plates, they showed an even more undifferentiated state. From these results, as a novel mechanism for maintaining HFSC, it was suggested that DCN functions as a stem cell niche component, and that the deficit of HFSC maintenance caused by a reduction in DCN expression could be a cause of age-related hair loss.
MeSH Terms
- Adult
- Adult Stem Cells
- Aged
- Aged, 80 and over
- Aging
- Alopecia
- Biopsy
- Cell Differentiation
- Cells, Cultured
- Child
- Decorin
- Female
- Gene Knockdown Techniques
- Hair Follicle
- Humans
- Keratin-15
- Male
- Middle Aged
- Primary Cell Culture
- RNA, Small Interfering
- Scalp
Keywords
- bulge
- decorin
- differentiation
- hair follicle stem cell
- stem cell niche
The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells (PCs). Here, we characterize the properties of the PC-DCN synapse in juvenile and adult mice and find that prolonged high-frequency stimulation leads to steady-state responses that become increasingly frequency independent within the physiological firing range of PCs in older animals, resulting in a linear relationship between charge transfer and activation frequency. We used a low-affinity antagonist to show that GABA -receptor saturation occurs at this synapse but does not underlie frequency-invariant transmission. We propose that PC-DCN synapses have two components of release: one prominent early in trains and another specialized to maintain transmission during prolonged activation. Short-term facilitation offsets partial vesicle depletion to produce frequency-independent transmission.
MeSH Terms
- Aging
- Animals
- Cerebellar Cortex
- Cerebellar Nuclei
- Mice
- Purkinje Cells
- Receptors, GABA-A
- Synapses
- Synaptic Transmission
Keywords
- Purkinje cells
- TPMPA
- cerebellum
- deep cerebellar nucleus
- presynaptic
- receptor saturation
- recovery from depression
- short-term facilitation
The human auditory system is highly susceptible to environmental and metabolic insults which further affect the biochemical and physiological milieu of the cells that may contribute to progressive, hearing loss with aging. The cochlear nucleus (CN) is populated by morphologically diverse types of neurons with discrete physiological and neurochemical properties. Between the dorsal and the ventral cochlear nucleus (DCN and VCN), the VCN is further sub-divided into the rostral (rVCN) and caudal (cVCN) sub-divisions. Although, information is available on the age related neurochemical changes in the mammalian CN similar reports on human CN is still sparse. The morphometry and semiquantitative analysis of intensity of expression of glial fibrillary acidic protein (GFAP), calcium binding proteins (calbindin, calretinin and parvalbumin), gamma amino butyric acid (GABA) and nicotinic acetyl choline receptor (nAchR) beta 2 immunostaining were carried out in all three sub-divisions of the human CN from birth to 90 years. There was increased GFAP immunoreactivity in decades 2 and 3 in comparison to decade 1 in the CN. But no change was observed in rVCN from decade 4 onwards, whereas intense staining was also observed in decades 5 and 6 in cVCN and DCN. All three calcium binding proteins were highly expressed in early to middle ages, whereas a significant reduction was found in later decades in the VCN. GABA and nAchR beta 2 expressions were unchanged throughout in all the decades. The middle age may represent a critical period of onset and progression of aging changes in the CN and these alterations may add to the deterioration of hearing responses in the old age.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Autopsy
- Calcium-Binding Proteins
- Child, Preschool
- Cochlear Nucleus
- Female
- Glial Fibrillary Acidic Protein
- Humans
- Infant
- Infant, Newborn
- Male
- Middle Aged
- Receptors, Nicotinic
- Young Adult
- gamma-Aminobutyric Acid
Keywords
- Aging changes
- Human auditory nucleus
- Image analysis
- Morphometry
- Neurotransmitters