scholarly journals Transcriptional landscape in rat intestines under hypobaric hypoxia

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11823
Author(s):  
Liuyang Tian ◽  
Zhilong Jia ◽  
Zhenguo Xu ◽  
Jinlong Shi ◽  
XiaoJing Zhao ◽  
...  

Oxygen metabolism is closely related to the intestinal homeostasis environment, and the occurrence of many intestinal diseases is as a result of the destruction of oxygen gradients. The hypobaric hypoxic environment of the plateau can cause dysfunction of the intestine for humans, such as inflammation. The compensatory response of the small intestine cells to the harsh environment definitely changes their gene expression. How the small intestine cells response the hypobaric hypoxic environment is still unclear. We studied the rat small intestine under hypobaric hypoxic conditions to explore the transcriptional changes in rats under acute/chronic hypobaric hypoxic conditions. We randomly divided rats into three groups: normal control group (S), acute hypobaric hypoxia group, exposing to hypobaric hypoxic condition for 2 weeks (W2S) and chronic hypobaric hypoxia group, exposing to hypobaric hypoxic condition for 4 weeks (W4S). The RNA sequencing was performed on the small intestine tissues of the three groups of rats. The results of principal component analysis showed that the W4S and W2S groups were quite different from the control group. We identified a total of 636 differentially expressed genes, such as ATP binding cassette, Ace2 and Fabp. KEGG pathway analysis identified several metabolic and digestive pathways, such as PPAR signaling pathway, glycerolipid metabolism, fat metabolism, mineral absorption and vitamin metabolism. Cogena analysis found that up-regulation of digestive and metabolic functions began from the second week of high altitude exposure. Our study highlights the critical role of metabolic and digestive pathways of the intestine in response to the hypobaric hypoxic environment, provides new aspects for the molecular effects of hypobaric hypoxic environment on intestine, and raises further questions about between the lipid metabolism disorders and inflammation.

Author(s):  
Tabita Prajasari ◽  
Chilmi Muhammad Zaim ◽  
Heri Suroto

The use of mesenchymal stem cells can add local improvements potential to enthesis tissue regeneration based on tropical activity through secretions of growth factors, cytokines, and vesicles (e.g. exosomes), collectively known as secretomes. This study aims to analyze secretomes characterization from adipose-derived mesenchymal stem cells seeded with enthesis tissue scaffold in hypoxic conditions and to analyze the influence of hypoxic environment to the characterization of secretomes. This is an in-vitro study using a Randomized Control Group Post-Test Only design. This study using Adipose Stem Cells (ASCs) were cultured in hypoxia (Oxygen 5%) and Normoxia (21%) condition. The scaffolds are fresh-frozen enthesis tissue and was seeded in the treatment group and compared to control. The evaluation of Scleraxis (Scx) and SRY-box (Sox9) was measured using ELISA on the 2nd, 4th, and 6th days. Comparison of Scx levels between each evaluation time showed a positive trend in a group with scaffold in hypoxia condition although it has no significant differences (p=0.085), with the highest level on day 6, that is 13,568 ng/ml. Conversely, the comparison of Sox9 showed significant differences (p=0.02) in a group with scaffold in hypoxia condition, with the highest level on day 4, that is 28,250 ng/ml. The use of enthesis scaffold seeded in adipose-derived mesenchymal stem cells in hypoxic conditions shows a positive trend as regenerative effort of injured enthesis tissue through Scleraxis and Sox9 secretomes induction.


2010 ◽  
Vol 5 (4) ◽  
pp. 497-508 ◽  
Author(s):  
Akinobu Nishimura ◽  
Masaaki Sugita ◽  
Ko Kato ◽  
Aki Fukuda ◽  
Akihiro Sudo ◽  
...  

Purpose:Recent studies have shown that low-intensity resistance training with vascular occlusion (kaatsu training) induces muscle hypertrophy. A local hypoxic environment facilitates muscle hypertrophy during kaatsu training. We postulated that muscle hypertrophy can be more efficiently induced by placing the entire body in a hypoxic environment to induce muscle hypoxia followed by resistance training.Methods:Fourteen male university students were randomly assigned to hypoxia (Hyp) and normoxia (Norm) groups (n = 7 per group). Each training session proceeded at an exercise intensity of 70% of 1 repetition maximum (RM), and comprised four sets of 10 repetitions of elbow extension and fexion. Students exercised twice weekly for 6 wk and then muscle hypertrophy was assessed by magnetic resonance imaging and muscle strength was evaluated based on 1RM.Results:Muscle hypertrophy was significantly greater for the Hyp-Ex (exercised fexor of the hypoxia group) than for the Hyp-N (nonexercised fexor of the hypoxia group) or Norm-Ex fexor (P < .05, Bonferroni correction). Muscle hypertrophy was significantly greater for the Hyp-Ex than the Hyp-N extensor. Muscle strength was significantly increased early (by week 3) in the Hyp-Ex, but not in the Norm-Ex group.Conclusion:This study suggests that resistance training under hypoxic conditions improves muscle strength and induces muscle hypertrophy faster than under normoxic conditions, thus representing a promising new training technique.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 951
Author(s):  
Shimeng Qiu ◽  
Tomoki Kabeya ◽  
Isamu Ogawa ◽  
Shiho Anno ◽  
Hisato Hayashi ◽  
...  

The evaluation of drug pharmacokinetics in the small intestine is critical for developing orally administered drugs. Caucasian colon adenocarcinoma (Caco-2) cells are employed to evaluate drug absorption in preclinical trials of drug development. However, the pharmacokinetic characteristics of Caco-2 cells are different from those of the normal human small intestine. Besides this, it is almost impossible to obtain primary human intestinal epithelial cells of the same batch. Therefore, human iPS cell-derived enterocytes (hiPSEs) with pharmacokinetic functions similar to human intestinal epithelial cells are expected to be useful for the evaluation of drug absorption. Previous studies have been limited to the use of cytokines and small molecules to generate hiPSEs. Dietary fibers play a critical role in maintaining intestinal physiology. We used gellan gum (GG), a soluble dietary fiber, to optimize hiPSE differentiation. hiPSEs cocultured with GG had significantly higher expression of small intestine- and pharmacokinetics-related genes and proteins. The activities of drug-metabolizing enzymes, such as cytochrome P450 2C19, and peptide transporter 1 were significantly increased in the GG treatment group compared to the control group. At the end point of differentiation, the percentage of senescent cells increased. Therefore, GG could improve the differentiation efficiency of human iPS cells to enterocytes and increase intestinal maturation by extending the life span of hiPSEs.


2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Rahadian Yudo Hartantyo ◽  
Helen Eko Putro ◽  
Epa Yohana Toga Torop ◽  
Laksmindra Fitria ◽  
Mulyati Mulyati

Several physiological alterations that arise in response to hypoxemia conditions when diving are intended to protect oxygen-sensitive organs from the hypoxic condition. Hippocampus, known for its central function in memory formation, is sensitive to hypoxic conditions. This research aimed to study the effect of voluntary diving exercise (VDE) on the hippocampus-dependent learning performance of rats. Rats were divided into control and diving groups, with swim and voluntary diving exercises every day for 60 days, respectively. Observation of memory consolidation was carried out using Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. In the MWM test, the escape latencies in the diving group were shorter than those in the control group. Consistent results were obtained in the MWM probe trial which the time spent in the target quadrant was significantly longer in the diving group. Moreover, the diving group spent more time exploring the novel object in the NOR test. Based on the results, we can conclude that 60 days VDE significantly improves hippocampus-dependent learning capacity in trained rats.


Animals ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 551 ◽  
Author(s):  
Ma ◽  
Wang ◽  
Gao ◽  
Liu ◽  
Zheng ◽  
...  

Female animals living in the Qinghai-Tibet Plateau have lower ovulation rates because of the hypoxic environment, however, the mechanism of hypoxia on animal follicles is unclear. In this study, the effects of hypoxia on bovine follicles were investigated using an in vitro follicular culture system. The results show that there was a significant decrease in follicular diameter from day 3 to day 6 in both hypoxia and hypoxia with estrogen (E2) and fulvestrant (ICI 182780) (hypoxia + E2 + ICI) groups, when compared with a normoxia group (p < 0.05). We also observed significant downregulation of ERα and FSHR, while upregulation of LHCGR expression in the hypoxia group and hypoxia + E2 + ICI groups compared to the normoxia group (p < 0.05). The expression of IGF1 gene was significantly downregulated in hypoxia + E2 + ICI group when compared to the hypoxia + E2 group (p < 0.05). The expression of HIF1A, ADAMTS1, VEGFA, and EDN2 were upregulated in both hypoxia and hypoxia + E2 + ICI groups in comparison to normoxia group (p < 0.05). Under hypoxic conditions, the addition of E2 resulted in a decrease of HIF1A protein but an increase of ERα protein in cultured bovine follicles (p < 0.05). In summary, hypoxia limits the growth of bovine follicle cultured in vitro through inhibition of ERα.


2020 ◽  
Vol 14 ◽  
Author(s):  
Ying Han ◽  
Liping Ding ◽  
Xiang Cheng ◽  
Ming Zhao ◽  
Tong Zhao ◽  
...  

The importance of hypoxia in the pathophysiology of inflammatory bowel disease (IBD) is increasingly being realized; also, hypoxia seems to be an important accelerator of brain inflammation, as has been reported by our group and others. IBD is a chronic intestinal disorder that leads to the development of inflammation, which is related to brain dysfunction. However, no studies have reported whether hypoxia is associated with IBD-induced neuroinflammation. Therefore, the objective of the present study was to determine whether hypoxia augments cerebral inflammation in a DSS-induced colitis mouse model. The mouse model was developed using 3% DSS for five days combined with exposure to hypoxic conditions (6,000 m) for two days. Mice were randomly divided into four groups: control group, DSS group, hypoxia group, and DSS plus hypoxia group. The results demonstrated that DSS combined with hypoxia resulted in up-regulation of colonic and plasmatic proinflammatory cytokines. Meanwhile, DSS plus hypoxia increased expression of Iba1, which is a marker of activated microglia, accompanied by increased expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the brain. Moreover, the expression of tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-5, was markedly downregulated. The current study provides new insight into how hypoxia exposure induces excessive inflammatory responses andpathophysiological consequences in the brain in a DSS-induced colitis model.


2013 ◽  
Vol 7 (1) ◽  
pp. 6-12 ◽  
Author(s):  
Takao Tsuji ◽  
Kazutetsu Aoshiba ◽  
Masayuki Itoh ◽  
Hiroyuki Nakamura ◽  
Kazuhiro Yamaguchi

Introduction: While tissue hypoxia is known to play a critical role in the process of vascular injury and repair, the effect of hypercapnia on this process remains uncertain. We investigated whether hypercapnia might influence endothelial cell wound healing under the influence of hypoxia. Materials and Methodology: Monolayers of human umbilical venous endothelial cells (HUVECs) were scratch-wounded and incubated under different levels of O2, CO2, and pH in the environment. Results: Inhibition of wound healing was observed in the HUVEC monolayers under the hypoxic condition as compared to the normoxic condition. Both hypercapnic acidosis and buffered hypercapnia, but not normocapnic acidosis improved the rate of wound healing under the influence of hypoxia. The beneficial effect of hypercapnia was associated with stimulation of cell proliferation, without effects on cell adhesion, migration or apoptosis. On the other hand, the stimulatory effect of hypercapnia on wound healing and cell proliferation was not noted under normoxic conditions. Conclusion: These results suggest that hypercapnia, rather than acidosis per se, accelerated the wound healing in HUVEC monolayers cultured under hypoxic conditions. The effect of hypercapnia on wound healing was due, at least in part, to the stimulation of cell proliferation by hypercapnia.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 426
Author(s):  
Angelina Stevany Regina Masengi ◽  
Fanny Septiani Farhan ◽  
Wawan Mulyawan ◽  
Mohamad Sadikin ◽  
Ninik Mudjihartini ◽  
...  

Background: Intermittent hypobaric hypoxia is suggested to possess a protective effect toward the hypoxic condition. The aim of this study is to analyze the expression of cytoglobin (Cygb), neuroglobin (Ngb) and the specific activity of acetylcholinesterase (AChE) in brain tissue as adaptive responses to intermittent hypobaric hypoxia. Methods: Twenty-five adult Sprague-Dawley male rats were divided into 5 groups: 1) The control group (normoxia); 2) group exposed to acute hypobaric hypoxia (AHH); 3) group exposed to hypobaric hypoxia (HH) on day-1 and re-exposed on day-8 (intermittent hypobaric hypoxia once or IHH1x); 4) group that is exposed to HH on day-1, re-exposed to HH on day-8 and day-15 (intermittent hypobaric hypoxia two times or IHH2x); 5) group exposed to HH on day-1, re-exposed to HH on day-8, day-15 and day-22 (intermittent hypobaric hypoxia 3x or IHH3x). Homogenized brain tissue was then measured and analyzed for Cygb and Ngb protein expression, and also AChE specific activity. Results: Cytoglobin and Ngb were decreased in the acute induction and increased significantly along with the increasing frequency of the IHH induction. There were significant differences in Cygb expression between IHH2x and IHH3x groups compared to normoxia group, and between IHH1x, IHH2x and IHH3x compared to AHH group. There were significant differences in Ngb expression between IHH2x and IHH3x groups compared to normoxia group and between IHH2x and IHH3x groups compared to AHH group. The specific activity of AChE was increased significantly since the first induction of AHH, but then decreased in IHH3x. There were significant differences in the specific activity of AChE between IHH2x and IHH3x groups compared to normoxia and between IHH2x and IHH3x groups compared to IHH1x groups. Conclusions: We conclude that IHH, especially IHH3x, seems to induce the protective adaptive response in the rat brain tissue through the changes of these three parameters.


2020 ◽  
Vol 19 (31) ◽  
pp. 2816-2823 ◽  
Author(s):  
Dario Di Stasio ◽  
Laura Mosca ◽  
Alberta Lucchese ◽  
Donatella Delle Cave ◽  
Hiromichi Kawasaki ◽  
...  

Background: microRNAs play a critical role in auto-immunity, cell proliferation, differentiation and cell death. miRNAs are present in all biological fluids, and their expression is essential in maintaining regular immune functions and preventing autoimmunity, whereas miRNA dysregulation may be associated with the pathogenesis of autoimmune and inflammatory diseases. Oral lichen planus (OLP) is an inflammatory disease mediated by cytotoxic T cells attack against epithelial cells. The present study aims to perform a specific microRNA expression profile through the analysis of saliva in this disease. Methods: The study group was formed by five patients (mean age 62.8±1.98 years; 3 females/2 males) affected by oral lichen planus and control group by five healthy subjects (mean age 59.8 years±2.3; 3 females/ 2 males); using a low-density microarray analysis, we recorded a total of 98 differentially expressed miRNAs in the saliva of patients with oral lichen planus compared to the control group. The validation was performed for miR-27b with qRT-PCR in all saliva samples of oral lichen planus group. Results: 89 miRNAs were up-regulated and nine down-regulated. In details, levels of miR-21, miR- 125b, miR-203 and miR15b were increased (p<0.001) in study group while levels of miR-27b were about 3.0-fold decreased compared to controls (p<0.001) of miR-27b expression in OLP saliva. QRTPCR validation confirmed the down regulation of miR-27b in all saliva samples. Conclusions: Collecting saliva samples is a non-invasive procedure and is well accepted by all patients. microRNAs can be readily isolated and identified and can represent useful biomarkers of OLP.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yeram Park ◽  
Deunsol Hwang ◽  
Hun-Young Park ◽  
Jisu Kim ◽  
Kiwon Lim

Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions. Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspired O2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspired O2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle. Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP; 1.9±0.9 vs. −0.3±0.9; p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1α protein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group. Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.


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