Редактирование: SPP1

Osteopontin precursor (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) [BNSP] [OPN] [PSEC0156]

==Publications==

{{medline-entry
|title=Dehydroepiandrosterone enhances decidualization in women of advanced reproductive age.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29397924
|abstract=To investigate the impact of the androgen precursor dehydroepiandrosterone (DHEA) on the decidualization of human endometrial stromal cells isolated from women of advanced reproductive age. In vitro study. University research institute. Proliferative phase primary human endometrial stromal fibroblasts (hESFs) were isolated from women of advanced reproductive age (n = 16; mean age, 44.7 ± 2.3). None of the women were receiving hormone therapy or had endometriosis. Isolated hESFs were decidualized in vitro by incubation with P (1 μM) and cAMP (0.1 mg/mL) in the presence, or absence, of DHEA (10 nM, 100 nM). Secretion of androgens was assessed by ELISA. Expression of decidualization markers and endometrial receptivity markers was assessed by quantitative polymerase chain reaction and ELISA. Decidualization responses were retained in hESF isolated from women of advanced reproductive age. Supplementation with DHEA increased androgen biosynthesis and concentrations of T and dihydrotestosterone were ∼3× greater after coincubation with DHEA compared with hESF stimulated with decidualization alone. Addition of DHEA to decidualized hESF increased expression of the decidualization markers [[IGFBP1]] and [[PRL]] and the endometrial receptivity marker [[SPP1]]. DHEA enhanced secretion of [[IGFBP1]], [[PRL]], and [[SPP1]] proteins maximally by day 8 of the decidualization time course concomitant with peak androgen concentrations. These novel results demonstrate DHEA can enhance in vitro decidualization responses of hESF from women of advanced reproductive age. Supplementation with DHEA during the receptive phase may augment endometrial function and improve pregnancy rates in natural or assisted reproductive cycles.
|mesh-terms=* Adult
* Biomarkers
* Cell Proliferation
* Cells, Cultured
* Decidua
* Dehydroepiandrosterone
* Dihydrotestosterone
* Female
* Fibroblasts
* Humans
* Insulin-Like Growth Factor Binding Protein 1
* Maternal Age
* Middle Aged
* Osteopontin
* Prolactin
* Reproductive Health
* Stromal Cells
* Time Factors
|keywords=* DHEA
* aging
* androgens
* decidualization
* fertility
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908781
}}
{{medline-entry
|title=Pathways of aging: comparative analysis of gene signatures in replicative senescence and stress induced premature senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28105936
|abstract=In culturing normal diploid cells, senescence may either happen naturally, in the form of replicative senescence, or it may be a consequence of external challenges such as oxidative stress. Here we present a comparative analysis aimed at reconstruction of molecular cascades specific for replicative (RS) and stressinduced senescence (SIPS) in human fibroblasts. An involvement of caspase-3/keratin-18 pathway and serine/threonine kinase Aurora A/ [[MDM2]] pathway was shared between RS and SIPS. Moreover, stromelysin/MMP3 and N-acetylglucosaminyltransferase enzyme [[MGAT1]], which initiates the synthesis of hybrid and complex Nglycans, were identified as key orchestrating components in RS and SIPS, respectively. In RS only, Aurora-B driven cell cycle signaling was deregulated in concert with the suppression of anabolic branches of the fatty acids and estrogen metabolism. In SIPS, Aurora-B signaling is deprioritized, and the synthetic branches of cholesterol metabolism are upregulated, rather than downregulated. Moreover, in SIPS, proteasome/ubiquitin ligase pathways of protein degradation dominate the regulatory landscape. This picture indicates that SIPS proceeds in cells that are actively fighting stress which facilitates premature senescence while failing to completely activate the orderly program of RS. The promoters of genes differentially expressed in either RS or SIPS are unusually enriched by the binding sites for homeobox family proteins, with particular emphasis on [[HMX1]], [[IRX2]], [[HDX]] and [[HOXC13]]. Additionally, we identified Iroquois Homeobox 2 ([[IRX2]]) as a master regulator for the secretion of [[SPP1]]-encoded osteopontin, a stromal driver for tumor growth that is overexpressed by both RS and SIPS fibroblasts. The latter supports the hypothesis that senescence-specific de-repression of [[SPP1]] aids in SIPS-dependent stromal activation. Reanalysis of previously published experimental data is cost-effective approach for extraction of additional insignts into the functioning of biological systems.
|mesh-terms=* Aging
* Bleomycin
* Cellular Senescence
* Cluster Analysis
* Gene Expression Profiling
* Gene Expression Regulation
* Humans
* Models, Biological
* Osteopontin
* Promoter Regions, Genetic
* Signal Transduction
* Stress, Physiological
* Transcriptome

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5249001
}}
{{medline-entry
|title=Autophagic homeostasis is required for the pluripotency of cancer stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27929731
|abstract=Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD  synthesis pathway [[NAMPT]] (nicotinamide phosphoribosyltransferase) and the transcription factor [[POU5F1]]/OCT4 (POU class 5 homeobox 1). First, our data show that the pharmacological inhibition and knockdown (K ) of [[NAMPT]] or the K  of [[POU5F1]] in human CSCs significantly decreased the expression of pluripotency markers [[POU5F1]], [[NANOG]] (Nanog homeobox) and [[SOX2]] (SRY-box 2), and upregulated the differentiation markers [[TUBB3]] (tubulin β 3 class III), [[CSN2]] (casein β), [[SPP1]] (secreted phosphoprotein 1), [[GATA6]] (GATA binding protein 6), T (T brachyury transcription factor) and [[CDX2]] (caudal type homeobox 2). Interestingly, these pluripotency-regulating effects of [[NAMPT]] and [[POU5F1]] were accompanied by contrasting levels of autophagy, wherein [[NAMPT]] K  promoted while [[POU5F1]] K  inhibited the autophagy machinery. Most importantly, any deviation from the basal level of autophagy, either increase (via rapamycin, serum starvation or Tat-beclin 1 [Tat-BECN1] peptide) or decrease (via [[ATG7]] or [[ATG12]] K ), strongly decreased the pluripotency and promoted the differentiation and/or senescence of CSCs. Collectively, these results uncover the link between the NAD  biosynthesis pathway, CSC transcription factor [[POU5F1]] and pluripotency, and further identify autophagy as a novel regulator of pluripotency of CSCs.
|mesh-terms=* Animals
* Autophagy
* Beclin-1
* Cell Differentiation
* Cell Proliferation
* Cell Survival
* Cellular Senescence
* Cytokines
* Doxorubicin
* Homeostasis
* Mice
* Models, Biological
* Neoplastic Stem Cells
* Nicotinamide Phosphoribosyltransferase
* Octamer Transcription Factor-3
* PTEN Phosphohydrolase
* Phosphorylation
* Pluripotent Stem Cells
* Proto-Oncogene Proteins c-akt
* Signal Transduction
* Sirolimus
* TOR Serine-Threonine Kinases
|keywords=* POU5F1/Oct4
* autophagy
* cancer stem cells
* differentiation
* pluripotency
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324853
}}
{{medline-entry
|title=Bone biology-related gingival transcriptome in ageing and periodontitis in non-human primates.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26859687
|abstract=Cellular and molecular immunoinflammatory changes in gingival tissues drive alveolar bone loss in periodontitis. Since ageing is a risk factor for periodontitis, we sought to identify age-related gingival transcriptome changes associated with bone metabolism in both healthy and in naturally occurring periodontitis. Adult (12-16 years) and aged (18-23 years) non-human primates (M. mulatta) (n = 24) were grouped into healthy and periodontitis. Gingival tissue samples were obtained and subjected to microarray analysis using the Gene Chip Macaque Genome Array. Gene expression profiles involved in osteoclast/osteoblast proliferation, adhesion and function were evaluated and compared across and between the age groups. QPCR was also performed on selected genes to validate microarray data. Healthy aged tissues showed a gene profile expression that suggest enhancement of osteoclastic adhesion, proliferation/survival and function ([[SPP1]], [[TLR4]], [[MMP8]] and TFEC) and impaired osteoblastic activity (SMEK3P and SMAD5). The gingival transcriptome in both adult and aged animals with naturally occurring periodontitis (FOS, [[IL6]], [[TLR4]], [[MMP9]], [[MMP10]] and [[SPP1]] genes) was consistent with a local inflammatory response driving towards bone/connective tissue destruction. A pro-osteoclastogenic gingival transcriptome is associated with periodontitis irrespective of age; however; a greater bone-destructive molecular environment is associated with ageing in healthy tissues.
|mesh-terms=* Adolescent
* Aging
* Alveolar Bone Loss
* Animals
* Gingiva
* Humans
* Macaca mulatta
* Periodontitis
* Transcriptome
* Young Adult
|keywords=* ageing
* gene expression
* non-human primates
* osteoclast
* periodontitis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844783
}}