scholarly journals Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

2009 ◽  
Vol 9 ◽  
pp. 313-319 ◽  
Author(s):  
Markus D. Schofer ◽  
S. Fuchs-Winkelmann ◽  
C. Wack ◽  
M. Rudisile ◽  
R. Dersch ◽  
...  

Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2–enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers.

2008 ◽  
Vol 197 (2) ◽  
pp. 309-314 ◽  
Author(s):  
Angélica Morales ◽  
Sumiko Morimoto ◽  
Lorenza Díaz ◽  
Guillermo Robles ◽  
Vicente Díaz-Sánchez

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an endothelial cell mitogen, expressed essentially in steroidogenic cells. Recently, the expression of EG-VEGF in normal human pancreas and pancreatic adenocarcinoma has been demonstrated. Epidemiologically, pancreatic carcinogenesis is more frequent in males than females, and given that androgen receptors and testosterone biotransformation have been described in pancreas, we hypothesized that testosterone could participate in the regulation of EG-VEGF expression. In this study, we investigated the regulation of EG-VEGF gene expression by testosterone in normal rat pancreatic tissue and rat insulinoma cells (RINm5F). Total RNA was extracted from rat pancreas and cultured cells. Gene expression was studied by real-time PCR and protein detection by immunohistochemistry. Serum testosterone was quantified by RIA. Results showed that EG-VEGF is expressed predominantly in pancreatic islets and vascular endothelium, as well as in RINm5F cells. EG-VEGF gene expression was lower in the pancreas of rats with higher testosterone serum levels. A similar effect that was reverted by flutamide was observed in testosterone-treated RINm5F cells. In summary, testosterone down-regulated EG-VEGF gene expression in rat pancreatic tissue and RINm5F cells. This effect could be mediated by the androgen receptor. To our knowledge, this is the first time that a direct effect of testosterone on EG-VEGF gene expression in rat pancreas and RINm5F cells is demonstrated.


2001 ◽  
Vol 170 (3) ◽  
pp. 555-564 ◽  
Author(s):  
AR Green ◽  
EL Parrott ◽  
M Butterworth ◽  
PS Jones ◽  
P Greaves ◽  
...  

This study compares the actions of oestradiol, tamoxifen, toremifene and raloxifene on enzyme and gene expression in uterine tissues of ovariectomised rats over 72 h. The time-course for the induction of ornithine decarboxylase by the compounds showed a rapid biphasic response, while for creatine kinase brain type (BB) there was a continued increase over 72 h. The efficacy of induction showed that, with both markers, oestradiol gave the highest induction level, followed by tamoxifen or toremifene and then raloxifene. RT-PCR demonstrated that all compounds decreased oestrogen receptor (ER) alpha, ERbeta and ERbeta2 gene expression, 8-24 h after the first dose, suggesting that down-regulation of ER is not the primary cause of the difference in efficacy between these compounds. Using cDNA arrays, expression of 512 genes was examined in the uteri of oestradiol- or tamoxifen-treated rats. Both compounds resulted in the up-regulation of heat-shock protein 27, telomerase-associated protein 1 and secretin. However, most surprising was the marked down-regulation of Wilms' tumour and retinoblastoma genes. We speculate that this may result in a loss of regulation of the transition from the G1 to the S phase in the cell cycle and may make cells more vulnerable to the carcinogenic effects of tamoxifen in this tissue.


2020 ◽  
Vol 21 (24) ◽  
pp. 9723
Author(s):  
Aleksandra Ryk ◽  
Aleksandra Łosiewicz ◽  
Arkadiusz Michalak ◽  
Wojciech Fendler

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.


1997 ◽  
Vol 82 (9) ◽  
pp. 3124-3127 ◽  
Author(s):  
Jan Frystyk ◽  
Thorbjørn Grøfte ◽  
Christian Skjærbæk ◽  
Hans Ørskov

Abstract Insulin-like growth factor (IGF) binding protein-I (IGFBP-1) has been suggested to regulate the availability of free IGF and the glucose lowering activity of the IGF-system in relation to fuel supply. Our recent observations of significant inverse correlations between free IGF-I and IGFBP-1 in cross-sectionally collected fasting serum samples support a possible physiological association between the peptides. To further study the impact of IGFBP-1 on free IGF levels and the possible participation of the IGF-system in glucose homeostasis, we studied the time course of changes in IGFBP-1 and free IGFs in 13 healthy subjects undergoing an oral glucose tolerance test (OGTT). Serum was collected every 30 min for 330 min. Glucose, insulin, and GH followed the expected patterns and had regained baseline levels at 270 min. Total IGF-I and free and total IGF-II remained unaltered. IGFBP-1 decreased significantly by 37–52% (P < 0.05) from 150 to 210 min, whereafter the concentration gradually increased by 75% to a level that tended to be above baseline (P = 0.052). Free IGF-I decreased by 29–38% (P < 0.05) at the end of the study (270–330 min). IGFBP-1 was inversely correlated to free IGF-I at baseline (r = −0.57; P < 0.05), as well as during the OGTT (r = 0.66; P < 0.0001). In contrast, free IGF-II was not correlated to IGFBP-1. Insulin, but not free IGF-I, correlated significantly with serum glucose (P < 0.05). These results extend our previous findings of an inverse correlation between free IGF-I and IGFBP-1 in cross-sectional studies to include longitudinal observations, and thus further substantiates the hypothesis that IGFBP-1 is an important determinant of free IGF-I in vivo. Significant changes in free IGF-I were observed only in the late postprandial phase, when glucose and insulin were fully normalized, demonstrating that free IGFs probably do not participate in glucoregulation to any significant degree during an oral glucose load in healthy subjects.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Saladrigas-García ◽  
M. D’Angelo ◽  
H. L. Ko ◽  
P. Nolis ◽  
Y. Ramayo-Caldas ◽  
...  

AbstractWeaning is a critical period in the life of pigs with repercussions on their health and welfare and on the economy of the swine industry. This study aimed to assess the effect of the commercial early weaning on gut microbiota, intestinal gene expression and serum metabolomic response via an integrated-omic approach combining 16S rRNA gene sequencing, the OpenArray gene expression technology and 1H-NMR spectroscopy. Fourteen piglets from different litters were sampled for blood, jejunum tissue and caecal content two days before (− 2d), and three days after (+ 3d) weaning. A clearly differential ordination of caecal microbiota was observed. Higher abundances of Roseburia, Ruminococcus, Coprococcus, Dorea and Lachnospira genera in weaned piglets compared to prior to weaning showed the quick microbial changes of the piglets’ gut microbiota. Downregulation of OCLN, CLDN4, MUC2, MUC13, SLC15A1 and SLC13A1 genes, also evidenced the negative impact of weaning on gut barrier and digestive functions. Metabolomic approach pinpointed significant decreases in choline, LDL, triglycerides, fatty acids, alanine and isoleucine and increases in 3-hydroxybutyrate after weaning. Moreover, the correlation between microbiota and metabolome datasets revealed the existence of metabolic clusters interrelated to different bacterial clusters. Our results demonstrate the impact of weaning stress on the piglet and give insights regarding the associations between gut microbiota and the animal gene activity and metabolic response.


2021 ◽  
Vol 11 (40) ◽  
pp. 154-155
Author(s):  
Capieaux Etienne ◽  
Donat De Groote ◽  
Pierre Dorfman ◽  
Maurice Jeaner

Background: Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and “low grade inflammation”, with the concomitant increased risk of cardiovascular events. As a chronic inflammatory process, MS results in a dysregulation of the cytokine profile. 2L®INFLAM, a Micro-immunotherapy (MI) medication formulated with highly diluted cytokines, is currently prescribed in Belgium for inflammatory diseases and potentially may be helpful for MS patients. Aims: To investigate the impact of 2L®INFLAM on selected gene expression markers (mRNA) in patients suffering from MS, in addition to biological and clinical parameters. Methodology: Four well characterized MS adult patients with stabilized body-weight were advised to take one capsule of 2L®INFLAM per day (by sublingual-oral route) for 6 months (composition in table 1). Concomitantly to biological and clinical examination, genes expression status was assessed by a DNA microarray technology (Oxygen™) comprising 200 genes involved mainly in oxidative stress and inflammation. Whole blood collection was performed before and after treatment (3-6 months) and mRNA levels measured. Gene expression was classified in 3 series (normally expressed, up or down-regulated) and genes related to diabetes predisposition were scored by using a proprietary Diascore (Probiox). Results: Before MI medication, a significant percentage of dysregulated genes (median: 16.3%) as well as a positive Diascore (median: 1.6) were noticed. Impressive correction of dysregulated genes (reaching 90% for one patient) was observed after 3 months of treatment (median: 2.3%) in addition to an improvement of Diascore in 3 MS patients out of 4 (median: 0.5). During the same period, both clinical and biological parameters remained unchanged. Conclusions: MS patients showing a high level of gene dysregulation efficiently normalized after 3 months of 2L®INFLAM (64%-90%), suggesting a biological regulatory effect of MI and a potential benefit of this medication for diabetic patients. Up and down-deregulated gene profiles were specific for each patient and not related to cytokine components of the formula. These preliminary data support the “domino effect” of MI sequential formula to restore in depth the immune homeostasis. DNA microarray technology may represent a promising tool for new provings as well as for biochemical comprehension of the “in vivo” effectiveness of highly diluted immune messengers. Table 1: 2L®INFLAM composition Compounds Dilutions Interleukin-1 (IL-1): 17 CH* Interleukin-1 Ra (IL-1 Ra): 3 CH Interleukin-2 (IL-2): 9 CH Interleukin-4 (IL-4): 7 CH Interleukin-6 (IL-6): 9 CH Interleukin-8 (IL-8): 9 CH Interleukin-10 (IL-10): 4 CH Interleukin-13 (IL-13): 9 CH Ciliary Neuro Trophic Factor (CNTF): 17 CH Leukemia Inhibitory Factor (LIF): 17 CH Oncostatine M (OSM): 9 CH Platelet Derived Growth Factor (PDGF): 5 CH Prostaglandine E2 (PgE2): 200 K** Rantes (Rantes): 17 CH Transforming Growth Factor beta(TGFβ): 5 CH Tumor Necrosis Factor α (TNFα): 17 CH SNA INFLAMa-01 18 C SNA INFLAMb-01 18 CH * CH: Centesimal Hahnemannian (1/100) ** K: Centesimal Korsakovian (1/100)


2020 ◽  
Vol 117 (29) ◽  
pp. 17438-17445
Author(s):  
Elena L. Peredo ◽  
Zoe G. Cardon

Among green plants, desiccation tolerance is common in seeds and spores but rare in leaves and other vegetative green tissues. Over the last two decades, genes have been identified whose expression is induced by desiccation in diverse, desiccation-tolerant (DT) taxa, including, e.g., late embryogenesis abundant proteins (LEA) and reactive oxygen species scavengers. This up-regulation is observed in DT resurrection plants, mosses, and green algae most closely related to these Embryophytes. Here we test whether this same suite of protective genes is up-regulated during desiccation in even more distantly related DT green algae, and, importantly, whether that up-regulation is unique to DT algae or also occurs in a desiccation-intolerant relative. We used three closely related aquatic and desert-derived green microalgae in the family Scenedesmaceae and capitalized on extraordinary desiccation tolerance in two of the species, contrasting with desiccation intolerance in the third. We found that during desiccation, all three species increased expression of common protective genes. The feature distinguishing gene expression in DT algae, however, was extensive down-regulation of gene expression associated with diverse metabolic processes during the desiccation time course, suggesting a switch from active growth to energy-saving metabolism. This widespread downshift did not occur in the desiccation-intolerant taxon. These results show that desiccation-induced up-regulation of expression of protective genes may be necessary but is not sufficient to confer desiccation tolerance. The data also suggest that desiccation tolerance may require induced protective mechanisms operating in concert with massive down-regulation of gene expression controlling numerous other aspects of metabolism.


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