Euglena extract suppresses adipocyte-differentiation in human adipose-derived stem cells.
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ABSTRACT:
SUBMITTER: Sugimoto R
PROVIDER: S-EPMC5813920 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Human adipose tissue‑derived stromal stem cells (HASCs) represent a promising regenerative resource for breast reconstruction and augmentation. However, the mechanisms involved in inducing its adipogenic differentiation remain to be fully elucidated. The present study aimed to comprehensively investigate the expression changes in mRNAs, microRNAs (miRNAs) and long non‑coding (lnc)RNAs during the adipogenic differentiation of HASCs, and screen crucial lncRNA‑miRNA‑mRNA interaction axes using microarray datasets GSE57593, GSE25715 and GSE61302 collected from the Gene Expression Omnibus database. Following pretreatment, differentially expressed genes (DEGs), miRNAs (DE‑miRNAs) or lncRNAs (DE‑lncRNAs) between undifferentiated and differentiated HASCs were identified using the Linear Models for Microarray data method. A protein‑protein interaction (PPI) network was constructed for the DEGs based on protein databases, followed by module analysis. The 'lncRNA‑miRNA‑mRNA' competing endogenous RNA (ceRNA) network was constructed based on the interactions between miRNAs and mRNAs, lncRNAs and miRNAs predicted by the miRWalk and lnCeDB databases. The underlying functions of mRNAs were predicted using the clusterProfiler package. In the present study, 905 DEGs, 36 DE‑miRNAs and 577 DE‑lncRNAs were screened between undifferentiated HASCs and differentiated adipocyte cells. PPI network analysis demonstrated that LEP may be a hub gene, which was also enriched in significant module 5. LEP was predicted to be involved in the Janus kinase‑signal transducer and activator of transcription signaling pathway, and the regulation of inflammatory response. The upregulation of LEP was regulated by downregulated hsa‑miRNA (miR)‑130b‑5p and hsa‑miR‑23a‑5p (or hsa‑miR‑302d‑3p). These miRNAs also respectively interacted with RP11‑552F3.9 (or RP11‑15A1.7), ultimately forming the ceRNA axes. In conclusion, the present study revealed that the RP11‑552F3.9 (RP11‑15A1.7)‑hsa‑miR‑130b‑5p/hsa‑miR‑23a‑5p (hsa‑miR‑302d‑3p)‑LEP interaction axes may be crucial for inducing the adipogenic differentiation of HASCs via involvement in inflammation.
| S-EPMC6471198 | biostudies-literature
Project description:IntroductionThe extract of pluripotent stem cells induces dedifferentiation of somatic cells with restricted plasticity.MethodsIn this study, we used the extract of human embryonic stem cells (hESC) to dedifferentiate adipose tissue-derived stem cells (ADSCs) and examined the impact of this reprogramming event on the dopaminergic differentiation of the cells. For this purpose, cytoplasmic extract of ESCs was prepared by repeated freezing and thawing cycles. The plasma membrane of hADSCs was reversibly permeabilized by streptolysin O (SLO), exposed to hESC extract, and resealed by a CaCl2-containing medium.ResultsAs revealed by qPCR analysis, expression of OCT4, SOX2, NANOG, LIN28A, and KLF4 mRNAs were downregulated in the ADSCs one week after extract incubation, while all mRNAs except for KLF4 were upregulated at the end of the second week. For dopaminergic differentiation, control and reprogrammed ADSCs were induced by a serum-free neurobasal medium containing B27 and a cocktail of sonic hedgehog (SHH), basic fibroblast growth factor (bFGF), fibroblastic growth factor 8 (FGF8), and brain-derived neurotrophic factor (BDNF) for 12 days. After differentiation, the expression levels of some neuronal and dopaminergic-related genes, including PAX6, NESTIN, NEFL, GLI1, LMXB1, EN1, NURR1, and TH, significantly increased in the reprogrammed ADSCs compared to the control group. On the whole, two weeks after reprogramming by ESC extract, ADSCs showed an improved dopaminergic differentiation potential.ConclusionThese findings suggest that the cytoplasmic extract of hESCs contains some regulatory factors which induce the expression of pluripotency-associated markers in somatic cells and that the exposure to ESC extract may serve as a simple and rapid strategy to enhance the plasticity of somatic stem cells for cell replacement therapy purposes.HighlightshADSCs have emerged as a valuable candidate for transplantation therapy of neurodegenerative diseases.Several studies have documented dopaminergic dedifferentiation of hADSCs.Implementing ADSCs towards a more pluripotent state using different strategies like somatic cell nuclear transfer.Plain language summaryThe extract of pluripotent stem cells induces dedifferentiation of somatic cells with restricted plasticity. In this study, we used the extract of hESC to dedifferentiate ADSCs and examined the impact of this reprogramming event on the dopaminergic differentiation of the cells. Cytoplasmic extract of ESCs was prepared by repeated freezing and thawing cycles. These cells express several neuron-specific genes, secrete several factors associated with neuroprotection, and exhibit differentiation into neural and glial cells in vitro. In recent years, several studies have documented dopaminergic differentiation of hADSCs.
| S-EPMC9682313 | biostudies-literature
Project description:Interruptin B has been isolated from Cyclosorus terminans, however, its pharamcological effect has not been fully identified. In the present study, the effects of interruptin B, from C. terminans, on brown adipocyte differentiation and glucose uptake in adipose‑derived stem cells (ASCs) were investigated. The results revealed that interruptin B dose‑dependently enhanced the adipogenic differentiation of ASCs, with an induction in the mRNA expression levels of peroxisome proliferator‑activated receptor (PPAR)‑α and PPAR‑γ. In addition, interruptin B efficiently increased the number and the membrane potential of mitochondria and upregulated the mRNA expression levels of uncoupling protein (UCP)‑1 and cyclooxygenase (COX)‑2, which are all predominantly expressed in brown adipocytes. Interruptin B increased glucose consumption in differentiated ASCs, accompanied by the upregulation in the mRNA expression levels of glucose transporter (GLUT)‑1 and GLUT‑4. The computational analysis of molecular docking, a luciferase reporter assay and surface plasmon resonance confirmed the marked binding affinity of interruptin B to PPAR‑α and PPAR‑γ (K(D) values of 5.32 and 0.10 µm, respectively). To the best of our knowledge, the present study is the first report to show the stimulatory effects of interruptin B on brown adipocyte differentiation and glucose uptake in ASCs, through its role as a dual PPAR‑α and PPAR‑γ ligand. Therefore, interruptin B could be further developed as a therapeutic agent for the treatment of diabetes.
| S-EPMC4769002 | biostudies-literature
Project description:Adipogenesis plays an important role in the regulation of whole-body energy homeostasis and is inextricably related to obesity. Several studies have highlighted the relevance of microRNAs in adipocyte differentiation, but the contributions of long non-coding RNAs (lncRNAs) are still largely uncharacterized. Here, we determined that lncRNA MIR31HG is related to adipocyte lineage commitment. We demonstrated that knockdown of MIR31HG inhibited adipocyte differentiation, whereas overexpression of MIR31HG promoted adipogenesis in vitro and in vivo. Furthermore, inhibition of MIR31HG reduced the enrichment of active histone markers, histone H3 lysine 4 trimethylation (H3K4me3) and acetylation (AcH3), in the promoter of the adipogenic-related gene, fatty acid binding protein 4 (FABP4), leading to suppression of its expression and adipogenesis. These results provide new insights into the molecular mechanisms of MIR31HG in terms of adipogenesis and may have implications for obesity and associated disorders.
| S-EPMC5556051 | biostudies-literature
Project description:MicroRNAs (miRs) are involved in several physiological processes, including chondrogenic differentiation, however, their expression and roles in the chondrogenic differentiation of human adipose‑derived stem cells (hADSCs) remain to be fully elucidated to date. Our previous study showed that miR‑1307‑3p was significantly downregulated during chondrogenic differentiation by microarray and northern blot analysis. The present study aimed to investigate the effects of miR‑1307‑3p on chondrogenic differentiation and the underlying mechanisms. First, the decreased expression of miR‑1307‑3p was confirmed by reverse transcription‑quantitative polymerase chain reaction analysis. Subsequently, gain‑ and loss‑of‑function of miR‑1307‑3p experiments showed that the overexpression of miR‑1307‑3p suppressed the deposition of cartilage matrix proteoglycans and decreased the expression of cartilage‑related markers, including sex determining region Y‑box 9, collagen type II α1 chain and aggrecan, whereas the knockdown of miR‑1307‑3p had the opposite effect. In addition, bone morphogenetic protein receptor type 2 (BMPR2) was identified as a target of miR‑1307‑3p. Further mechanistic investigations showed that miR‑1307‑3p attenuated the chondrogenic differentiation of hADSCs at least partly by inhibiting BMPR2‑mothers against decapentaplegic signaling pathways. In conclusion, the findings revealed that miR‑1307‑3p inhibited the chondrogenic differentiation of hADSCs by targeting BMPR2 and its downstream signaling pathway, which may provide novel therapeutic clues for the treatment of cartilage injury.
| S-EPMC6202098 | biostudies-literature
Project description:PURPOSE:Adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (AMSCs) is critical to many disease-related disorders, such as obesity and diabetes. Studies have demonstrated that miRNA-138 (miR-138) is closely involved in adipogenesis. However, the mechanisms affected by miR-138 remain unclear. This work aimed to investigate interactions between miR-138 and lipoprotein lipase (LPL), a key lipogenic enzyme, in AMSCs. MATERIALS AND METHODS:Human AMSCs (hAMSCs) isolated from human abdomen tissue were subjected to adipogenic differentiation medium. Quantitative real-time polymerase chain reaction and Western blot assay were applied to measure the expressions of miR-138, LPL, and the two adipogenic transcription factors cytidine-cytidine-adenosine-adenosine-thymidine enhancer binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ). The relationship between miR-138 and LPL was predicted utilizing the miRTarBase database and validated by dual luciferase reporter assay. RESULTS:Showing increases in C/EBPα and PPARγ expression levels, hAMSCs were induced into adipogenic differentiation. During adipogenesis of hAMSCs, miR-138 expression was significantly downregulated. Overexpression of miR-138 by transfection inhibited hAMSCs adipogenic differentiation in vitro. Mechanically, LPL was a target of miR-138. LPL expression was upregulated during adipogenesis of hAMSCs, and this upregulation was reversed by miR-138 overexpression. Functionally, silencing of LPL by transfection exerted similar inhibition of the expressions of C/EBPα and PPARγ. Meanwhile, LPL ectopic expression was able to partly abolish the suppressive effect of miR-138 overexpression on adipogenic differentiation of hAMSCs. CONCLUSION:Upregulation of miR-138 inhibits adipogenic differentiation of hAMSCs by directly downregulating LPL.
| S-EPMC6881710 | biostudies-literature
Project description:Tissue engineering using suitable mesenchymal stem cells (MSCs) shows great potential to regenerate bone defects. Our previous studies have indicated that human amnion-derived mesenchymal stem cells (HAMSCs) could promote the osteogenic differentiation of human bone marrow mesenchymal stem cells (HBMSCs). Human adipose-derived stem cells (HASCs), obtained from adipose tissue in abundance, are capable of multi-lineage differentiation. In this study, the effects of HAMSCs on osteogenic and angiogenic differentiation of HASCs were systematically investigated. Proliferation levels were measured by flow cytometry. Osteoblastic differentiation and mineralization were investigated using chromogenic alkaline phosphatase activity (ALP) activity substrate assays, Alizarin red S staining, real-time polymerase chain reaction (real-time PCR) analysis of osteogenic marker expression, and Western blotting. We found that HAMSCs increased the proliferation and osteoblastic differentiation of HASCs. Moreover, enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial cells (HUVECs) tube formation suggested HAMSCs enhanced angiogenic potential of HASCs via secretion of increased vascular endothelial growth factor (VEGF). Thus, we conclude that HAMSC might be a valuable therapeutic approach to promote HASCs-involved bone regeneration.
| S-EPMC5636128 | biostudies-literature
Project description:Placental extract, which contains various bioactive compounds, has been used as traditional medicine. Many studies have demonstrated additional applications of placental extract and provided a scientific basis for the broad spectrum of its effects. We have previously reported that porcine placental extract (PPE) strongly suppresses adipogenesis in a 3T3-L1 preadipocyte cell line, inhibiting differentiation. This study aimed to examine the effect of PPE on the accumulation of lipid droplets (LD) in adipose-derived mesenchymal stromal/stem cells (ASC). The study findings revealed that PPE decreased the size of LD during the differentiation of ASC into mature adipocytes. RT-qPCR analysis revealed that PPE increased the gene expression of lysosomal acid lipase A (Lipa), a lipolysis-related gene, in ASC-differentiated adipocytes. However, no differences were noted in the adipocyte differentiation markers (Pparg, Cebpa, and Adipoq), or the adipogenesis-related genes (Dgat1, Dgat2, Fasn, Soat1, and Soat2). In addition, PPE promoted autophagosome formation, which was partially co-localized with the LD, indicating that PPE accelerated the degradation of LD by inducing autophagy (termed lipophagy) during the differentiation of ASC into mature adipocytes. These results suggest that the use of PPE may be a potential novel treatment for regulating adipogenesis for the treatment of obesity.
| S-EPMC10655368 | biostudies-literature
Project description:Human adipose-derived stem cells (ASCs) may differentiate into cardiomyocytes and this provides a source of donor cells for tissue engineering. In this study, we evaluated cardiomyogenic differentiation protocols using a DNA demethylating agent 5-azacytidine (5-aza), a modified cardiomyogenic medium (MCM), a histone deacetylase inhibitor trichostatin A (TSA) and co-culture with neonatal rat cardiomyocytes. 5-aza treatment reduced both cardiac actin and TropT mRNA expression. Incubation in MCM only slightly increased gene expression (1.5- to 1.9-fold) and the number of cells co-expressing nkx2.5/sarcomeric alpha-actin (27.2% versus 0.2% in control). TSA treatment increased cardiac actin mRNA expression 11-fold after 1 week, which could be sustained for 2 weeks by culturing cells in cardiomyocyte culture medium. TSA-treated cells also stained positively for cardiac myosin heavy chain, alpha-actin, TropI and connexin43; however, none of these treatments produced beating cells. ASCs in non-contact co-culture showed no cardiac differentiation; however, ASCs co-cultured in direct contact co-culture exhibited a time-dependent increase in cardiac actin mRNA expression (up to 33-fold) between days 3 and 14. Immunocytochemistry revealed co-expression of GATA4 and Nkx2.5, alpha-actin, TropI and cardiac myosin heavy chain in CM-DiI labelled ASCs. Most importantly, many of these cells showed spontaneous contractions accompanied by calcium transients in culture. Human ASC (hASC) showed synchronous Ca(2+) transient and contraction synchronous with surrounding rat cardiomyocytes (106 beats/min.). Gap junctions also formed between them as observed by dye transfer. In conclusion, cell-to-cell interaction was identified as a key inducer for cardiomyogenic differentiation of hASCs. This method was optimized by co-culture with contracting cardiomyocytes and provides a potential cardiac differentiation system to progress applications for cardiac cell therapy or tissue engineering.
| S-EPMC3823119 | biostudies-literature
Project description:BackgroundInjection of adipose-derived stem cells (ASCs) is a promising treatment for facial contour deformities. However, its treatment mechanisms remain largely unknown. The study aimed to explain the molecular mechanisms of adipogenic differentiation from ASCs based on the roles of long noncoding RNAs (lncRNAs).MethodsDatasets of mRNA-lncRNA (GSE113253) and miRNA (GSE72429) expression profiling were collected from Gene Expression Omnibus database. The differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs) between undifferentiated and adipocyte differentiated human ASCs were identified using the Linear Models for Microarray Data method. DELs related co-expression and competing endogenous RNA (ceRNA) networks were constructed. Protein-protein interaction (PPI) analysis was performed to screen crucial target genes.ResultsA total of 748 DEGs, 17 DELs and 51 DEMs were identified. A total of 13 DELs and 279 DEGs with Pearson correlation coefficients > 0.9 and p-value < 0.01 were selected to construct the co-expression network. A total of 151 interaction pairs among 112 nodes (10 DEMs; eight DELs; 94 DEGs) were obtained to construct the ceRNA network. By comparing the lncRNAs and mRNAs in two networks, five lncRNAs (SNHG9, LINC02202, UBAC2-AS1, PTCSC3 and myocardial infarction associated transcript (MIAT)) and 32 genes (i.e., such as phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), protein tyrosine phosphatase receptor type B (PTPRB)) were found to be shared. PPI analysis demonstrated PIK3R1 , forkhead box O1 (FOXO1; a transcription factor) and estrogen receptor 1 (ESR1) were hub genes, which could be regulated by the miRNAs that interacted with the above five lncRNAs, such as LINC02202-miR-136-5p-PIK3R1, LINC02202-miR-381-3p-FOXO1 and MIAT-miR-18a-5p-ESR1. LINC02202 also could directly co-express with PIK3R1. Furthermore, PTPRB was predicted to be modulated by co-expression with LINC01119.ConclusionMIAT, LINC02202 and LINC01119 may be potentially important, new lncRNAs associated with adipogenic differentiation of ASCs. They may be involved in adipogenesis by acting as a ceRNA or co-expressing with their targets.
| S-EPMC6733242 | biostudies-literature