Редактирование: SP1 (раздел)

==Publications==

{{medline-entry
|title=The effects and mechanism of collagen peptide and elastin peptide on skin aging induced by D-galactose combined with ultraviolet radiation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32717457
|abstract=The content of collagen and elastin occupies a large proportion of skin evaluation, and collagen peptide ([[CP]]) and elastin peptide (EP) are widely used drugs, which have anti-inflammatory effects. In addition, [[CP]] and EP can also be used as therapeutic agents for skin repair. However, previous studies have never thoroughly verified the effects of oral administration of [[CP]] and EP on skin repair. To study the effects and mechanism of oral administration of [[CP]] and EP on skin aging induced by combinatorial treatment with D-galactose and ultraviolet radiation. In animal experiments, the combined oral administration of [[CP]] and EP increased the contents of collagen and elastin in animal skin, accompanying with significantly upregulated expression of hyaluronic acid and hydroxyproline, as well as significantly reduced expression of MMP-3 and IL-1α. In addition, the combined therapy also significantly increased the expression of seven collagen and elastin synthesis-related factors including IGF-1, [[LOX]], [[SMAD2]], JNK, [[SP1]], TβRII and TGF-β. Oral administration of [[CP]] and EP can repair skin aging induced by the combined treatment with D-galactose and ultraviolet radiation and the effects of [[CP]] and EP appeared synergistic.

|keywords=* Collagen
* D-galactose
* Elastin
* Skin aging
* Ultraviolet
|full-text-url=https://sci-hub.do/10.1016/j.jphotobiol.2020.111964
}}
{{medline-entry
|title=Identification of key genes and transcription factors in aging mesenchymal stem cells by DNA microarray data.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30641220
|abstract=Mesenchymal stem cells ([[MSC]]s) are multipotent cells that can be widely used in stem cell therapy. However, few studies have revealed the potential mechanisms of the changes in aging [[MSC]]. In this study, microarray data GSE35955 was downloaded from the Gene Expression Omnibus database. Then limma package in R was used to filtrate differentially expressed genes (DEGs), Transcription factors ([[TF]]s) were predicted by DCGL package. After predicting [[TF]]s, protein-protein interaction (PPI) network and [[TF]]-mediated transcriptional regulation network were constructed. The functional and pathway enrichment analysis of screened DEGs, hub genes and [[TF]]s were conducted by the DAVID. Totally 156 up-regulated DEGs and 343 down-regulated DEGs were obtained. 6 hub genes ([[CTNNB1]], [[PPP2R1A]], [[FYN]], [[MAPK1]], [[PIK3C2A]] and [[EP300]]) were obtained from PPI network. 11 [[TF]]s (CREB1, [[[[CUX1]]]], [[EGR1]], [[EP300]], [[FOXC1]], [[HSF2]], [[MEF2A]], [[PLAU]], [[SP1]], [[STAT1]] and USF1) for DEGs were predicted and 2 highly scored co-expression relationships ([[EP300]]-[[PPP2R1A]] and [[STAT1]]-[[FOXC1]]) were acquired from the [[TF]]-mediated transcriptional regulation network. The discovery of the hub genes, [[TF]]s and pathways might contribute to the understanding of genetic and molecular functions of aging-related changes in [[MSC]]. Further validation studies on genes and [[TF]]s such as [[CTNNB1]], [[FYN]], [[PPP2R1A]], [[MAPK1]], [[EP300]] and related biological processes and pathways, including adherens junction, DNA damage caused from oxidative stress, attribution of telomere, [[MSC]] differentiation and epigenetic regulation, are urgent for clinical prevention and treatment.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Gene Expression Profiling
* Gene Expression Regulation
* Humans
* Mesenchymal Stem Cells
* Middle Aged
* Mitogen-Activated Protein Kinase 1
* Oligonucleotide Array Sequence Analysis
* Protein Interaction Maps
* Protein Phosphatase 2
* Proto-Oncogene Proteins c-fyn
* Transcription Factors
* beta Catenin
|keywords=* Differentially expressed genes
* Enrichment analysis
* Gene Expression Omnibus
* Hub genes
* Microarray analysis
* Protein-protein interaction network
* Transcriptional regulatory network
|full-text-url=https://sci-hub.do/10.1016/j.gene.2018.12.063
}}
{{medline-entry
|title=Downregulation of [[CITED2]] contributes to TGFβ-mediated senescence of tendon-derived stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28084522
|abstract=Tendon-derived stem cells (TDSCs) are multipotent adult stem cells with potential applications in tendon and tendon-bone junction repair. However, cellular characteristics change during in vitro passaging. Therefore, elucidation of the molecular and cellular mechanisms of tendon aging will be essential for the development of TDSC-based therapies. The aim of this study is to investigate the effect of [[CITED2]], a nuclear regulator and transforming growth factor β2 (TGFβ2) on TDSC proliferation and senescence by comparing cells derived from Achilles tendon biopsies of young individuals (Y-TDSC) with those of older patients (O-TDSC). Our results showed that [[CITED2]] mRNA and protein expression levels were significantly higher in Y-TDSCs than in O-TDSCs and O-TDSCs displayed decreased proliferation and increased senescence compared with Y-TDSCs. Furthermore, high levels of [[CITED2]] protein expression in Y-TDSCs correlated with the downregulation of [[SP1]] and p21 and the upregulation of [[MYC]], potentially indicating the mechanism by which [[CITED2]] upregulates TDSC proliferation. TGFβ2 was found to downregulate the expression of the [[CITED2]] gene and knockdown of [[CITED2]] abolished the effect of TGFβ2 on TDSC proliferation and senescence. Thus, the downregulation of [[CITED2]] contributes to TGFβ-mediated senescence providing an insight into the molecular and cellular mechanisms that contribute to tendon aging and degeneration. Our findings may aid the development of cell-based therapies for tendon repair.
|mesh-terms=* Achilles Tendon
* Adult
* Aged
* Biopsy
* Blotting, Western
* Cell Proliferation
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p21
* Down-Regulation
* Gene Knockdown Techniques
* Humans
* Proto-Oncogene Proteins c-myc
* RNA, Messenger
* Real-Time Polymerase Chain Reaction
* Repressor Proteins
* Sp1 Transcription Factor
* Stem Cells
* Trans-Activators
* Transforming Growth Factor beta
* Up-Regulation
|keywords=* CITED2
* Cell proliferation
* Senescence
* Tendon-derived stem cells
* Transforming growth factor β2
|full-text-url=https://sci-hub.do/10.1007/s00441-016-2552-1
}}
{{medline-entry
|title=Homocysteine accelerates senescence of endothelial cells via DNA hypomethylation of human telomerase reverse transcriptase.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25359865
|abstract=Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity. When compared with primary human umbilical vein endothelial cells grown under standard conditions, ECs with chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages. Interestingly, homocysteine-stimulated but not angiotensin II-stimulated ECs senescence could be reversed by hypermethylation induced by folic acid or s-adenosylmethionine supplementation. Meanwhile, homocysteine promoted the shortening of telomere length specifically related to restoration of hTERT transcriptional expression and CCCTC-binding factor binding sites with hTERT promoter hypomethylation, as detected by quantitative real-time polymerase chain reaction, Western blot, methylation-specific polymerase chain reaction, and bisulfite sequencing assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation results showed that homocysteine-reduced telomere activity and homocysteine-induced EC senescence might contribute to hTERT promoter demethylation by increasing CCCTC-binding factor repression and interfering in the [[SP1]] binding to the demethylated hTERT promoter, which might relate with reduced of DNA methyltransferase 1. Furthermore, the CCCTC-binding factor-dependent mechanism of homocysteine-reduced hTERT expression via DNA demethylation was confirmed in aortic endothelia of mice with hyperhomocysteine levels. CCCTC-binding factor and [[SP1]] cross talk may contribute to homocysteine-reduced hTERT DNA methylation and expression in endothelial senescence.
|mesh-terms=* Angiotensin II
* Animals
* Binding Sites
* CCCTC-Binding Factor
* Cells, Cultured
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p16
* Cyclin-Dependent Kinase Inhibitor p21
* DNA Methylation
* Disease Models, Animal
* Folic Acid
* Gene Expression Regulation, Enzymologic
* Homocysteine
* Human Umbilical Vein Endothelial Cells
* Humans
* Hyperhomocysteinemia
* Male
* Mice, Inbred C57BL
* Promoter Regions, Genetic
* RNA Interference
* Repressor Proteins
* S-Adenosylmethionine
* Sp1 Transcription Factor
* Telomerase
* Telomere
* Telomere Shortening
* Time Factors
* Transfection
* Tumor Suppressor Protein p53
|keywords=* aging
* endothelial cells
* homocysteine
* telomerase reverse transcriptase, human
|full-text-url=https://sci-hub.do/10.1161/ATVBAHA.114.303899
}}
{{medline-entry
|title=A functional and genetic analysis of [[SOD2]] promoter variants and their contribution to age-related hearing loss.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23500038
|abstract=Genetic variation in superoxide dismutase 2 ([[SOD2]]) is implicated in several ageing pathologies and with noise-induced hearing loss. Here, we have investigated the role of [[SOD2]] promoter variants in age related hearing loss (ARHL). Putative regulatory variants identified in the [[SOD2]] promoter using bioinformatics were functionally evaluated in an inner-ear-derived cell line (OC-2). Variants with effects on transcription factor binding were then tested in association studies in discovery and replication cohorts (London ARHL and ELSA cohorts, n=2177). The rs5746092 (-38C>G) and rs2758343 (-299C>A) SNPs alter the affinity of the [[SOD2]] promoter for AP-2α and [[SP1]] respectively. Evidence of an association between the -38C>G SNP and ARHL was detected in the London cohort only; p=0.0436, OR=1.35 [1.05-1.73]. This effect was strongest in males reporting family history of ARHL (p=0.0095) and was independent of reported noise exposure. The rs2758343 (-299C>A) rSNP was found to be in complete LD with the well characterised functional variant rs4880 (Ala16Val) and was not associated with hearing loss. This study describes the effect of common [[SOD2]] promoter variation on [[SOD2]] promoter regulation and links it to ARHL risk in men. However, due to lack of replication, this association should be regarded as suggestive only.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Cell Line
* Cohort Studies
* Hearing Loss
* Humans
* Male
* Middle Aged
* Polymorphism, Single Nucleotide
* Response Elements
* Sp1 Transcription Factor
* Superoxide Dismutase
* Transcription Factor AP-2

|full-text-url=https://sci-hub.do/10.1016/j.mad.2013.02.009
}}