scholarly journals AQP3 Facilitates Proliferation and Adipogenic Differentiation of Porcine Intramuscular Adipocytes

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 453
Author(s):  
Xiaoyu Wang ◽  
Jing Yang ◽  
Ying Yao ◽  
Xin’E Shi ◽  
Gongshe Yang ◽  
...  
Keyword(s):  
Adipogenic Differentiation ◽  
Animal Products ◽  
Akt Phosphorylation ◽  
Cell Cycle Genes ◽  
Protein Levels ◽  
Water Glycerol ◽  
Differentiation And Proliferation ◽  
Intramuscular Fat Content

The meat quality of animal products is closely related to the intramuscular fat content. Aquaglyceroporin (AQP) defines a class of water/glycerol channels that primarily facilitate the passive transport of glycerol and water across biological membranes. In this study, the AQP3 protein of the AQP family was mainly studied in the adipogenic function of intramuscular adipocytes in pigs. Here, we found that AQP3 was increased at both mRNA and protein levels upon adipogenic stimuli in porcine intramuscular adipocytes in vitro. Western blot results showed knockdown of AQP3 by siRNA significantly suppressed the expression of adipogenic genes (PPARγ, aP2, etc.), repressed Akt phosphorylation, as well as reducing lipid accumulation. Furthermore, deletion of AQP3 by siRNA significantly downregulated expression of cell cycle genes (cyclin D, E), and decreased the number of EdU-positive cells as well as cell viability. Collectively, our data indicate that AQP3 is of great importance in both adipogenic differentiation and proliferation in intramuscular adipocytes, providing a potential target for modulating fat infiltration in skeletal muscles.

A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants

Blood ◽  
2011 ◽  
Vol 118 (6) ◽  
pp. 1699-1709 ◽  
Author(s):  
Isabelle Ligi ◽  
Stéphanie Simoncini ◽  
Edwige Tellier ◽  
Paula Frizera Vassallo ◽  
Florence Sabatier ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Profile Analysis ◽  
Preterm Neonates ◽  
Akt Phosphorylation ◽  
Protein Levels ◽  
Increased Risk ◽  
The Impact

Abstract Low birth weight (LBW) is associated with increased risk of cardiovascular diseases at adulthood. Nevertheless, the impact of LBW on the endothelium is not clearly established. We investigate whether LBW alters the angiogenic properties of cord blood endothelial colony forming cells (LBW-ECFCs) in 25 preterm neonates compared with 25 term neonates (CT-ECFCs). We observed that LBW decreased the number of colonies formed by ECFCs and delayed the time of appearance of their clonal progeny. LBW dramatically reduced LBW-ECFC capacity to form sprouts and tubes, to migrate and to proliferate in vitro. The angiogenic defect of LBW-ECFCs was confirmed in vivo by their inability to form robust capillary networks in Matrigel plugs injected in nu/nu mice. Gene profile analysis of LBW-ECFCs demonstrated an increased expression of antiangiogenic genes. Among them, thrombospondin 1 (THBS1) was highly expressed at RNA and protein levels in LBW-ECFCs. Silencing THBS1 restored the angiogenic properties of LBW-ECFCs by increasing AKT phosphorylation. The imbalance toward an angiostatic state provide a mechanistic link between LBW and the impaired angiogenic properties of ECFCs and allows the identification of THBS1 as a novel player in LBW-ECFC defect, opening new perspectives for novel deprogramming agents.

scholarly journals Prognostic Relevance and Function of MSX2 in Colorectal Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jiancheng Liu ◽  
Huaying An ◽  
Wei Yuan ◽  
Qiang Feng ◽  
Lianzhen Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Stage ◽  
Total Mortality ◽  
Test Analysis ◽  
Akt Phosphorylation ◽  
Protein Levels ◽  
Patients With Diabetes ◽  
Chi Squared ◽  
And Function

Colorectal cancer patients with diabetes had the high risks of total mortality. High expression of MSX2 is related to development of diabetes. There are few reports about the clinical implications and function of MSX2 in colorectal cancer (CRC). The purpose of this study is to investigate the relationship between the expression of MSX2 and clinical relevance and discover the possible mechanism of MSX2 in the development of CRC. Compared with adjacent tissues, the expression of MSX2 was higher in tumor tissues in both mRNA and protein levels (P<0.01). Kaplan-Meier survival analysis showed that high mRNA expression of MSX2 was associated with short survival time (P=0.013). Chi-squared test analysis indicated that MSX2 expression was related to tumor size (P=0.04), tumor locus (P=0.025), clinical stage (P<0.001), tumor invasion (P=0.003), lymphatic metastasis (P=0.01), and distant metastasis (P=0.033). In vitro experiments demonstrated that knockdown of MSX2 expression attenuated cell proliferation and invasion, promoted cell cycle arrest and apoptosis, and inactivated Akt phosphorylation. In conclusion, MSX2 played a crucial role in the progression of CRC and may be a potential novel prognostic factor and therapeutic target for CRC therapy. Our work may provide certain enlightenment for investigating the mechanism of MSX2 in the process of diabetes.

scholarly journals miR-26b-5p/TCF-4 Controls the Adipogenic Differentiation of Human Adipose-derived Mesenchymal Stem Cells

2020 ◽  
Vol 29 ◽  
pp. 096368972093441 ◽  
Author(s):  
Yadong Luo ◽  
Huan Ji ◽  
Yan Cao ◽  
Xu Ding ◽  
Meng Li ◽  
...  
Keyword(s):  
Adipogenic Differentiation ◽  
Negative Regulator ◽  
Immunofluorescent Staining ◽  
Luciferase Reporter ◽  
Bioinformatics Analyses ◽  
Protein Levels ◽  
Pathway Gene ◽  
Adipocytic Differentiation ◽  
The Impact

In this study, we assessed the ability of miR-26b-5p to regulate T cell factor 4 (TCF-4) expression and thereby control human adipose-derived mesenchymal stem cell (hADMSC) adipogenic differentiation. Adipogenic medium was used to induce hADMSC differentiation over a 6-d period. The ability of miR-26b-5p to interact with the TCF-4 mRNA was confirmed through both predictive bioinformatics analyses and luciferase reporter assays. Immunofluorescent staining was used to visualize the impact of miR-26b-5p inhibition or overexpression on TCF-4 and β-catenin levels in hADMSCs. Further functional analyses were conducted by transfecting these cells with siRNAs specific for TCF-4 and β-catenin. Adipogenic marker and Wnt/β-catenin pathway gene expression levels were assessed via real-time polymerase chain reaction and western blotting. β-catenin localization was assessed via immunofluorescent staining. As expected, our adipogenic media induced the adipocytic differentiation of hADMSCs. In addition, we confirmed that TCF-4 is an miR-26b-5p target gene in these cells, and that protein levels of both TCF-4 and β-catenin were reduced when these cells were transfected with miR-26b-5p mimics. Overexpression of this microRNA also enhanced hADMSC adipogenesis, whereas TCF-4 and β-catenin overexpression inhibited this process. The enhanced hADMSC adipogenic differentiation that was observed following TCF-4 or β-catenin knockdown was partially reversed when miR-26b-5p expression was inhibited. We found that miR-26b-5p serves as a direct negative regulator of TCF-4 expression within hADMSCs, leading to inactivation of the Wnt/β-catenin pathway and thereby promoting the adipogenic differentiation of these cells in vitro.

scholarly journals Jingui Shenqi Pills Regulate Bone-Fat Balance in Murine Ovariectomy-Induced Osteoporosis with Kidney Yang Deficiency

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Qi Shang ◽  
Wenhua Zhao ◽  
Gengyang Shen ◽  
Xiang Yu ◽  
Zhida Zhang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Bone Microarchitecture ◽  
Adipogenic Differentiation ◽  
Sham Operation ◽  
Akt Phosphorylation ◽  
Bilateral Ovariectomy ◽  
Tissue Area ◽  
Kidney Yang Deficiency ◽  
Selection Of

Jingui Shenqi Pills (JGSQP) have been a staple of traditional Chinese medicine for thousands of years, used primarily as a treatment for kidney yang deficiency (KYD). In vitro analyses of JGSQP revealed strong induction of osteogenic differentiation and inhibition of adipogenic differentiation in bone-marrow-derived mesenchymal stem/stromal cells. However, the mechanisms by which JGSQP regulate the bone-fat balance in murine ovariectomy-induced osteoporosis with KYD have not been reported. Materials and Methods. Two-month-old female C57BL/6 mice were divided randomly into three groups: those receiving a sham operation (Sham); those undergoing bilateral ovariectomy and selection of KYD syndrome (Model); and those subjected to both bilateral ovariectomy and KYD syndrome selection for 8 weeks, followed by JGSQP treatment for 4 weeks (JGSQP). In the Sham and Model groups, mice were given the same dose of distilled water orally for 4 weeks. Animals from all three groups were euthanised at the 12th week. Vertebral microarchitecture and histomorphology were examined by micro-CT and H&E staining, respectively. In addition, we examined the mRNA expression of Akt, Wnt10b, Osterix (Osx), Fndc5, PPARγ, and Fabp4, as well as the protein of AKT, phosphorylation-AKT (p-AKT), BMP2, COL1A1, and FNDC5. Results. JGSQP treatment improved bone microarchitecture and mitigated histomorphological damage relative to the Model group. The osteoblast number (Ob.N/BS) and area (Ob.S/BS) were increased, whereas adipocyte number (adipocyte/tissue area) and area (adipocyte area/tissue area) were decreased in the JGSQP group. JGSQP treatment reduced the mRNA expression of Akt and adipogenesis-related genes (Fndc5, PPARγ, and Fabp4) while promoting osteogenesis-related genes (Wnt10b and Osx) mRNA expression. Additionally, the expression of p-AKT, BMP2, and COL1A1 proteins was increased and FNDC5 protein expression was decreased after JGSQP treatment. Conclusions. JGSQP treatment reversed murine ovariectomy-induced osteoporosis with KYD by controlling bone-fat balance via AKT pathway.

scholarly journals Potential Application of Cord Blood-Derived Stromal Cells in Cellular Therapy and Regenerative Medicine

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Simone Maria Kluth ◽  
Teja Falk Radke ◽  
Gesine Kogler
Keyword(s):  
Regenerative Medicine ◽  
Cord Blood ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
Adipogenic Differentiation ◽  
Cell Populations ◽  
Differentiation Potential ◽  
Differentiation And Proliferation

Neonatal stromal cells from umbilical cord blood (CB) are promising alternatives to bone marrow- (BM-) derived multipotent stromal cells (MSCs). In comparison to BM-MSC, the less mature CB-derived stromal cells have been described as a cell population with higher differentiation and proliferation potential that might be of potential interest for clinical application in regenerative medicine. Recently, it has become clear that cord blood contains different stromal cell populations, and as of today, a clear distinction between unrestricted somatic stromal cells (USSCs) and CB-MSC has been established. This classification is based on the expression of DLK-1, HOX, and CD146, as well as functional examination of the adipogenic differentiation potential and the capacity to support haematopoiesis in vitro and in vivo. However, a marker enabling a prospective isolation of the rare cell populations directly out of cord blood is yet to be found. Further analysis may help to reveal even more subpopulations with different properties, which could be useful for the directed application of these cells in preclinical models.

scholarly journals LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice

Bone Research ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Yiming Lei ◽  
Xuekun Fu ◽  
Pengyu Li ◽  
Sixiong Lin ◽  
Qinnan Yan ◽  
...  
Keyword(s):  
Bone Mass ◽  
Adipogenic Differentiation ◽  
Mutant Mice ◽  
Lim Domain ◽  
Double Knockout ◽  
Single Mutant ◽  
Protein Levels ◽  
Proliferative Zone ◽  
Column Formation

Abstract The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell–extracellular matrix interaction and adhesion. Here, we report that deleting Pinch1 in limb mesenchymal stem cells (MSCs) and Pinch2 globally (double knockout; dKO) in mice causes severe chondrodysplasia, while single mutant mice do not display marked defects. Pinch deletion decreases chondrocyte proliferation, accelerates cell differentiation and disrupts column formation. Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone (PZ) chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone (HZ) chondrocytes. Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes, reduces bone formation, and increases bone resorption, leading to low bone mass. In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes. Through its C-terminal region, Pinch1 interacts with Smad2/3 proteins. Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells (BMSCs). Pinch loss reduces TGF-β-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs. Interestingly, compared to those from single mutant mice, BMSCs from dKO mice express dramatically lower protein levels of β-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity. Finally, ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening. Collectively, our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms.

scholarly journals Adipogenic differentiation of human adipose-derived mesenchymal stem cells regulated by microRNA-26b-5p/TCF-4

2020 ◽  
Author(s):  
Yadong Luo ◽  
Huan Ji ◽  
Yan Cao ◽  
Xu Ding ◽  
Meng Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Negative Regulator ◽  
Protein Levels ◽  
Interfering Rna ◽  
The Relationship ◽  
Low Expression

Abstract Background: Our study was designed to investigate the role of miR-26b-5p on TCF-4, affecting the adipogenic differentiation of human adipose-derived mesenchymal stem cells (hADMSCs). METHODS: The adipogenic differentiation of hADMSCs was induced by adipogenic medium for 6 days (d). Bioinformatic and dual-luciferase analyses were used to confirm the relationship between TCF-4 and miR-26b-5p. Immunofluorescence was used to detect the effect of miR-26b-5p on TCF-4 and β-catenin in hADMSCs transfected with miR-26b-5p mimic and inhibitor. Mimic, inhibitor, and small interfering RNA (siRNA) transfected in hADMSCs to against LEF1 and β-catenin. Quantitative real-time PCR and western blotting were used to examine the adipogenic markers and Wnt/β-catenin pathway at the mRNA and protein levels, respectively. Immunofluorescence was performed to locate β-catenin. RESULTS: hADMSCs could differentiate toward adipocytes by the adipogenic medium. The results of bioinformatic and dual-luciferase analyses show that TCF-4 is a potential target of miR-26b-5p. The immunofluorescence intensity of TCF4 and β-catenin were inhibited by miR-26b-5p in hADMSCs. Overexpression of miR-26b-5p promotes the adipogenic differentiation of hADMSCs. Overexpression of TCF-4 and β-catenin inhibits the adipogenic differentiation of hADMSCs. The adipogenic differentiation of hADMSCs that promoted by knocking down TCF4 could be weakened by low-expression of miR-26b-5p. The stimulative effect of β-catenin low-expression in adipogenic differentiation was inhibited by miR-26b-5p inhibitor. Conclusions: miR-26b-5p is a negative regulator to inhibit TCF-4 directly, and then inactivated Wnt/β-catenin pathway, which promotes the adipogenic differentiation of hADMSCs in vitro.

Bioactive Peptides Sensitize Cells to Anticancer Effects of Oxaliplatin in Human Colorectal Cancer Xenografts in Nude Mice

2019 ◽  
Vol 26 (7) ◽  
pp. 512-522
Author(s):  
Xian Li ◽  
Long Xia ◽  
Xiaohui Ouyang ◽  
Qimuge Suyila ◽  
Liya Su ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Nude Mice ◽  
Low Dose ◽  
Bioactive Peptides ◽  
Human Colorectal Cancer ◽  
Short Term ◽  
Hct 116

<P>Background: Despite new agent development and short-term benefits in patients with Colorectal Cancer (CRC), metastatic CRC cure rates have not improved due to high rates of oxaliplatin resistance and toxicity. There is an urgent need for effective tools to prevent and treat CRC and reduce morbidity and mortality of CRC patients. Exploring the effects of bioactive peptides on the antitumor to CRC was of vital importance to the clinical application. </P><P> Objective: This study aimed to investigate the therapeutic impact of Anticancer Bioactive Peptides (ACBP) on anticancer effect of oxaliplatin (LOHP) in human colorectal cancer xenografts models in nude mice. </P><P> Methods: HCT-116 cells were cultured in vitro via CCK-8 assays and the absorbance was measured at 450 nm. Apoptosis and cell cycle were assessed by Flow Cytometry (FCM) in vitro. HCT-116 human colorectal cancer cells inoculated subcutaneously in nude mice of treatment with PBS (GG), ACBP, LOHP, ACBP+LOHP (A+L) in vivo. The quality of life was assessed by dietary amount of nude mice, the weight of nude mice, inhibition rates, tumor weight and tumor volume. Immunohistochemistry and RT-qPCR method was conducted to determine the levels of apoptosisregulating proteins/genes in transplanted tumors. </P><P> Results: ACBP induced substantial reductions in viable cell numbers and apoptosis of HCT116 cells in combined with LOHP in vitro. Compared with the control GG group, ACBP combined low dose oxaliplatin (U) group demonstrated significantly different tumor volume, the rate of apoptosis, the expression levels of Cyt-C, caspase-3,8,9 proteins and corresponding RNAs (P<0.05). The expression of pro-apoptotic proteins in the cytoplasm around the nucleus was significantly enhanced by ACBP. Short term intermittent use of ACBP alone indicted a certain inhibitory effect on tumor growth, and improve the quality of life of tumor bearing nude mice. </P><P> Conclusion: ACBP significantly increased the anti-cancer responses of low dose oxaliplatin (L-LOHP), thus, significantly improving the quality of life of tumor-bearing nude mice.</P>

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