scholarly journals Comparative study of some skin and lung fibroblast genes expression of rats of different age

Comparative study of the expression of three different groups of genes and their protein products amount in the culture of skin fibroblasts from Wistar rats of different ages (2 weeks, 1, 12 and 24 months) was carried out. The traits of similarities and differences in age dynamics for vimentin, vinculin, decorin have been found. These three genes, the products of which participate in intracellular interactions (vimentin) and interactions of cytoskeleton proteins with components of the extracellular matrix, are characterized by an increase in the expression with age both in the skin and in the lungs. They are expressed much stronger in the skin than in the lungs. The amount of their products fluctuates without any single direction. The most active is the expression of vinculin, both in the skin and in the lungs; the amount of the product is also the maximal for it. The least effective is the expression of the vimentin gene in the lungs of two-week-old rats. For the gene expression of fibroblast growth factors 1, 2 and 8, significant differences have been found in their changes in ontogenesis. The first two of them, whose products stimulate the synthesis of one of the most common and important forms of collagen 1, are minimally expressed in old animals, both in the skin and in the lungs. The gene of fibroblast growth factor 8 is expressed in both tissues significantly weaker than the genes of factors 1 and 2. The direction of age-related expression of factor 8 is opposite to that which is inherent for the expression of genes 1 and 2. As for the protein product, its amount is maximal in 1 month, and in the skin significantly increased in the second half of ontogenesis. Some homeobox genes, the HOX genes (2, 4, 5, 6, 7), have been studied. They are most important for the early stages of ontogenesis due to their influence on organogenesis, especially in the embryonic period. In general, both their expression and the product amount decrease, especially in old animals. HOX 5 is most expressed among these genes in the lungs and in the skin. The results obtained are discussed in connection with the functional and tissue characteristics of the studied genes and their products.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1288-1288
Author(s):  
Julia Starkova ◽  
Blanka Vicenova ◽  
Roman Krejci ◽  
Harry A. Drabkin ◽  
Jan Trka

Abstract Abstract 1288 Poster Board I-310 Homeodomain (HOX) genes encode transcription factors important for embryonic development. They are involved in normal hemopoiesis regulation and likely also in leukemogenesis as a result of translocations and other aberrations present in leukemias. In previous work Drabkin et al. demonstrated that HOX gene expression patterns differentiate major cytogenetic groups in acute myeloid leukemias. In this study we focused on HOX gene expression in pediatric acute lymphoblastic leukemias (ALL). We were interested if certain HOX genes or expression pattern could distinguish subpopulations of ALL. We analyzed the expression pattern of 21 HOX genes from HOXA and HOXB clusters and non-cluster HOX genes, CDX1 and CDX2 using qRT-PCR approach. We looked at 54 patients chosen according to phenotypic (T-ALL, BCP-ALL), prognostic (PGR – prednisone good responders, PPR – prednisone poor responders) and genotypic (BCR/ABL, MLL/AF4, TEL/AML1, hyperdiploid) characteristics. Overall analysis comparing all studied groups showed that HOXA7 (Kruskal-Wallis test p=0.000045), HOXA3 (p=0.000098), HOXB3 (p=0.00015), HOXA4 (p=0.000619) and HOXB4 (p=0.001925) genes were differently expressed among groups. Wilcoxon signed-rank test, a non-parametric statistical analysis comparing two groups against each other, showed that HOXA3, A4 and B3 distinguish BCP-ALL (w/o fusion gene) and T-ALL. Interestingly, particular HOX genes expression showed significant difference among the groups: HOXA7 gene is significantly downregulated in hyperdiploid ALL (p=0.03) compared to all other subgroups. Furthermore, HOXB7 gene is specifically upregulated in TEL/AML-positive patients (p=0.0048 vs BCP-ALL w/o fusion gene) and CDX2 is downregulated in BCR/ABL-positive patients (p=0.001 vs hyperdiploid; p=0.006 vs TEL/AML1; p=0.03 vs MLL/AF4). Suprisingly, TEL/AML1-positive patients have similar expression of HOXA1-A4 as T-ALL patients. HOX genes expression pattern seemed to differ in MLL/AF4-positive patients according to the age at diagnosis. Three patients younger than 2 months at presentation clustered together in clear contrast to the MLL/AF4-positive patient diagnosed at the age of 13 years with secALL who presented with very low overall expression of all HOX genes. Next, we looked for diversity and similarity between groups. We determined how many HOX genes were expressed differently (p<0.05) and similarly (p=1.0) between particular ALL subtypes. The most outlying couples were T-ALL vs PPR (11 genes differently expressed), T-ALL vs PGR (9 genes) and T-ALL vs TEL/AML1 (6 genes). In contrast, the closest groups were BCR/ABL vs PPR, MLL/AF4 vs T-ALL and MLL/AF4 vs PPR. Our data demonstrate that BCP-ALL (w/o known fusion gene) can be distinguished from T-ALL by the HOX gene expression (in particular HOXA3, HOXB3, HOXA4). Like in AML, expression pattern differs also among the major cytogenetical subgroups of ALL. On the other hand, within the BCP-ALL subgroup, no expression difference was found between patients with good (PGR) and poor (PPR) response to the initial steroid therapy which is known to be an excellent predictor of outcome. HOX genes of interest emerged from our analysis: low expression of HOXA7 in hyperdiploid ALL, highly expressed HOXB7 in TEL/AML1-positive ALL and specifically downregulated CDX2 in BCR/ABL-positive ALL. Age-related differences in expression in MLL/AF4-positive ALL seem to link the expression pattern rather with the relative maturity of the cell undergoing (pre)malignant transformation than with the specific changes caused by the leukemogenesis itself. This hypothesis must be tested in comparison to the HOX genes expression in sorted subtypes of normal T and B precursors. This work was supported by MSM0021620813, IGA NR/9526 and GACR 301/08/P532. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Lubov Kozhevnikova ◽  
Irina Sukhanova ◽  
NP Semenova ◽  
Alena Efimova ◽  
Sergey Kryzhanovskii

Abstract Age is the main risk factor for cardiovascular disease development. Understanding of mechanism underlying the vascular and myocardial ageing is necessary both for prevention and for treatment of age-associated diseases. The research aimed to evaluate age-related changes in the transcriptional activity of genes involved in the regulation of Ca2 + signalling – IP3R, RyR, and modulators of their activity CaM and Epac in blood vessels and myocardium of rats of both sexes.Gene expression was evaluated according to the mRNA content of the test protein relative to the β-actin mRNA content. It is proven that rats of both sexes develop unidirectional changes in the expression of genes encoding IP3Rs and RyR2, and different ones in the expression of protein genes modulating their activity – CaM and Epac depending on the sex of animals. In the vessels of old rats (24 months) of both sexes the relative level of mRNA for IP3R type 2 and 3 was reduced and not changed for IP3R1, and significantly increased for RyR2 receptors compared to these indicators in young rats (4 months). In the aorta of old females the relative mRNA content for CaM and Epac1 was reduced and not changed for Epac2. On the contrary, the expression of Epac1 and Epac2 was increased by 67% and 50% respectively compared to similar indicators in young rats (4 months) and rests unchanged for CaM which indicates gender differences in the violation of subtle mechanisms for modulating the activity of RyR2 and IP3Rs in blood vessels. Old rats showed significant changes in myocardium. In older males, the expression of RyR2,IP3R1,2, 3 increases in the left ventricle, RyR2 and IP3R1 – in the left atrium, and RyR2 and IP3R3 – in the right atrium. Unlike males, the mRNA content for RyR2, IP3R1, 2, 3 was significantly lower in the left ventricle of females than in young animals. High levels of IP3R1 and IP3R3 expression were detected in the right atrium of senior females, and IP3R3 expression was detected in the left atrium. The expression of IP3R2 was unchanged in all parts of the female heart. In the myocardium of old rats of both sexes the expression of CaM and Epac2 proteins increased significantly. The revealed age differences in the transcriptional activity of genes involved in the regulation of intracellular Ca2 + signalling at the level of IP3Rs-and RyR2-mediated mechanisms suggest that with the increasing life expectancy males are significantly more likely to develop myocardial hypertrophy and heart rhythm disorders than females.


2018 ◽  
Author(s):  
Ludwik Gasiorowski ◽  
Andreas Hejnol

Background: Hox genes encode a family of homeodomain containing transcription factors that are clustered together on chromosomes of many Bilateria. Some bilaterian lineages express these genes during embryogenesis in spatial and/or temporal order according to their arrangement in the cluster, a phenomenon referred to as collinearity. Expression of Hox genes is well studied during embryonic and larval development of numerous species; however, relatively few studies focus on the comparison of pre- and postmetamorphic expression of Hox genes in animals with biphasic life cycle. Recently, the expression of Hox genes was described for embryos and larvae of Terebratalia transversa, a rhynchonelliformean brachiopod, which possesses distinct metamorphosis from planktonic larvae to sessile juvenile. During premetamorphic development, T. transversa does not exhibit spatial collinearity and several of its Hox genes are recruited for the morphogenesis of novel structures. In our study we determined expression of Hox genes in post-metamorphic juveniles of T. transversa in order to examine metamorphosis-related changes of expression patterns and to test if Hox genes are expressed in the spatially collinear way in the postmetamorphic juveniles. Results: Hox genes are expressed in a spatially non-collinear manner in juveniles, generally showing similar patterns as ones observed in competent larvae: genes labial and Post1 are expressed in chaetae-related structures, sex comb reduced in the shell forming epithelium, whereas Lox5 and Lox4 in dorso-posterior epidermis. After metamorphosis expression of genes proboscipedia, Hox3, Deformed and Antennapedia becomes restricted to, respectively, shell musculature, prospective hinge rudiments, and pedicle musculature and epidermis. Conclusions: All developmental stages of T. transversa, including postmetamorphic juveniles, exhibit a spatial non-collinear Hox genes expression with only minor changes observed between pre- and postmetamorphic stages. Our results are concordant with morphological observation that metamorphosis in rhynchonelliformean brachiopods, despite being rapid, is rather gradual. The most drastic changes in Hox genes expression patterns observed during metamorphosis could be explained by the inversion of the mantle lobe, which relocates some of the more posterior larval structures into the anterior edge of the juveniles. Cooption of Hox genes for the morphogenesis of novel structures is even more pronounced in post-metamorphic brachiopods when compared to larvae.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1916-P
Author(s):  
REBECCA L. SCALZO ◽  
GRAHAME F. EVANS ◽  
SARA E. HULL ◽  
LESLIE KNAUB ◽  
LORI A. WALKER ◽  
...  

Author(s):  
Małgorzata Żychowska ◽  
Agata Grzybkowska ◽  
Mariusz Zasada ◽  
Anna Piotrowska ◽  
Danuta Dworakowska ◽  
...  

Abstract Background In this study, we investigated the effects of supplementation and exercise on the expression of genes associated with inflammation like CCL2, CRP, IL1, IL6, IL10 mRNA in elderly women. Methods Twenty four participants divided randomly into two groups were subjected to 6 weeks of the same health training program (three times per week). SUP group (supplemented, n = 12, mean age 72.8 ± 5.26 years and mean body mass 68.1 ± 8.3 kg) received 1000 mg of Vitamin C/day during the training period, while CON group (control, n = 12, mean age 72.4 ± 5.5 years and body mass 67.7 ± 7.5 kg) received placebo. Results No significant changes in IL-1, IL-6, IL-10 and CRP mRNA were observed within and between groups. However, there was a clear tendency of a decrease in IL-6 (two-way ANOVA, significant between investigated time points) and an increase in IL-10 mRNA noted in the supplemented group. A significant decrease in CCL2 mRNA was observed only in the CON group (from 2^0.2 to 2^0.1, p = 0.01). Conclusions It can be concluded, that 6 weeks of supplementation and exercise was too short to obtain significant changes in gene expression in leukocytes, but supplementation of 1000 mg vitamin C positively affected IL-6 and IL-10 expression – which are key changes in the adaptation to training. However, changes in body mass, IL1 and CCL2 were positive in CON group. It is possible that Vitamin C during 6 weeks of supplementation could have different effects on the expression of individual genes involved in the immune response. Trial registration Retrospectively registered. 


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Homer-Bouthiette ◽  
L. Xiao ◽  
Marja M. Hurley

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.


1990 ◽  
Vol 126 (3) ◽  
pp. 461-466 ◽  
Author(s):  
M. N. Sillence ◽  
R. G. Rodway

ABSTRACT The effects of trenbolone acetate (TBA) on growth and on plasma concentrations of corticosterone were examined in male and female rats. At 5 weeks of age, rats were injected with TBA (0·8 mg/kg) dissolved in peanut oil, or with oil alone, daily for 10 days. In female rats, TBA caused an increase in weight gain (20–38%), a reduction in adrenal weight (19%) and a reduction in plasma concentrations of corticosterone (55%). In contrast, TBA-treated male rats showed no significant increase in weight gain, no significant change in adrenal weight and no reduction in plasma concentrations of corticosterone. The mechanism by which adrenal activity was suppressed in TBA-treated female rats was examined and the response compared with that to testosterone. Female rats (8 weeks old) were injected daily either with oil vehicle, TBA (0·8 mg/kg) or testosterone propionate (0·8 mg/kg). Testosterone increased weight gain (24%), but the growth response to TBA treatment was significantly greater (97%). A reduction in plasma concentrations of corticosterone (45%) was again observed in response to TBA. However, testosterone increased plasma concentrations of corticosterone (52%) above those of control values. Neither androgen affected plasma concentrations of ACTH. Finally, the effects of TBA were examined in 6-week-old female rats, to characterize further the apparent age-related increase in responsiveness. The growth response of 6-week-old rats (60–74%) was intermediate between that seen in 5- and 8-week-old animals. It is concluded that part of the anabolic activity of TBA may be related to a reduction in circulating concentrations of corticosterone. The effect of TBA on corticosterone concentrations differs from that of the natural androgen, testosterone, and does not appear to be mediated by a reduction in plasma concentrations of ACTH. Journal of Endocrinology (1990) 126, 461–466


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