Heat shock factor protein 2 (HSF 2) (Heat shock transcription factor 2) (HSTF 2) [HSTF2]

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Identification of key genes and transcription factors in aging mesenchymal stem cells by DNA microarray data.

Mesenchymal stem cells (MSCs) 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 (TFs) were predicted by DCGL package. After predicting TFs, 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 TFs 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 TFs (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, TFs and pathways might contribute to the understanding of genetic and molecular functions of aging-related changes in MSC. Further validation studies on genes and TFs 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


Nutrition and water temperature regulate the expression of heat-shock proteins in golden pompano larvae (Trachinotus ovata, Limmaeus 1758).

Understanding fish larval development is of a great interest for aquaculture production efficiency. Identifying possible indicators of fish larvae stress could improve the production and limit the mortality rate that larval stage is subjected to. Heat-shock proteins (HSPs) and heat-shock factors (HSFs) are well known as indicators of response to many kinds of stressor (e.g., environmental, morphological, or pathological changes). In this study, golden pompano larvae were raised at different temperatures (23 °C, 26 °C, and 29 °C), as well as three different diets (Artemia nauplii unenriched, Artemia nauplii enriched with Nannochloropsis sp., and Artemia nauplii enriched with Algamac 3080), and the expression of HSP60, HSP70, HSF1, HSP2, and GRP94 were monitored. While stress genes were widely expressed in the larval tissues, HSP60 and HSP70 were principally from the gills and heart; HSF1 principally from the muscle, brain, and heart; and GRP94 principally from the head kidney and spleen. Golden pompano larvae were found to be more sensitive to thermal changes at later larval stage, and 29 °C was showed to likely be the best condition for golden pompano larval development. Nannochloropsis sp.-enriched Artemia nauplii treatment was found to be the most appropriate feed type with moderate relative expressions of HSP60, HSP70, HSF1, HSF2, and GRP94.

MeSH Terms

  • Adaptation, Physiological
  • Aging
  • Animal Feed
  • Animal Nutritional Physiological Phenomena
  • Animals
  • Cloning, Molecular
  • Diet
  • Fishes
  • Gene Expression Regulation
  • Heat-Shock Proteins
  • Larva
  • Temperature

Keywords

  • Fish larvae
  • Gene expression
  • Heat-shock protein
  • Nutrition
  • Temperature


Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins.

Sirtuins are proteins that connect energy metabolism, oxidative stress and aging. Expression of heat shock proteins (Hsps) is regulated by heat shock factors (HSFs) in response to various environmental and physiological stresses, such as oxidative stress. Oxidative stress accumulates during aging which makes cells more prone to DNA damage. Although many experimental animal models have been designed to study the effects of knockdown or overexpression of sirtuins, HSFs and Hsps, little is known about how aging per se affects their expression. Here we study the impact of intrinsic aerobic capacity, aging and voluntary exercise on the levels of sirtuins, HSFs and Hsps in skeletal muscle. We studied the protein levels of sirtuins (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7), HSF1, HSF2, Hsp10, Hsp27 and Hsp70 before and after one-year of voluntary running intervention of rat strains selectively bred for intrinsic aerobic exercise capacity; high capacity runners (HCR) and low capacity runners (LCR) differ by more than 30% for median lifespan. This setup enabled us to discern the effects of inborn aerobic capacity, aging and exercise activity on the protein levels of sirtuins, HSFs and Hsps in skeletal muscle. Our results revealed that the longer lived HCR rats had higher SIRT3, HSF1 and HSF2 contents in skeletal muscle (gastrocnemius, p < 0.05) than LCRs. Neither aging nor voluntary running had a significant effect on the studied sirtuin proteins. Aging significantly increased the protein levels of HSF1, HSF2 and Hsp27 (p < 0.05). Our finding of elevated SIRT3 levels in HCR rats is in line with previous studies; SIRT3 in general is linked to elevated fatty acid oxidation and oxidative phosphorylation, which previously have been associated with metabolic profile of HCRs. HSF1, HSF2 and Hsp27 levels increased with aging, showing that aged muscles responded to aging-related stress. Our study shows for the first time that SIRT3 protein level is linked to high inborn aerobic capacity, and may be directly interconnected to longevity.

MeSH Terms

  • Aging
  • Animals
  • Body Weight
  • Citrate (si)-Synthase
  • Energy Intake
  • Female
  • Heat-Shock Proteins
  • Muscle, Skeletal
  • Oxidative Stress
  • Physical Conditioning, Animal
  • Rats, Inbred Strains
  • Running
  • Sirtuins

Keywords

  • aging
  • oxidative stress
  • physical activity
  • sirtuin
  • skeletal muscle