scholarly journals Single-minded 2 is required for left-right asymmetric stomach morphogenesis

Development ◽  
2021 ◽  
Author(s):  
Brent H. Wyatt ◽  
Nirav M. Amin ◽  
Kristen Bagley ◽  
Dustin Wcisel ◽  
Michael K. Dush ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Down Syndrome ◽  
Digestive Tract ◽  
Birth Defects ◽  
Drosophila Gene ◽  
Molecular Events ◽  
Critical Phase ◽  
Related Transcription Factor ◽  
Dose Dependent ◽  
Stomach Epithelium

The morphogenesis of left-right (LR) asymmetry is a critical phase of organogenesis. In the digestive tract, the development of anatomical asymmetry is first evident in the leftward curvature of the stomach. To elucidate the molecular events that shape this archetypal laterality, we performed transcriptome analyses of the left versus right sides of the developing stomach in frog embryos. Besides the known LR gene pitx2, the only gene found to be expressed asymmetrically throughout all stages of curvature was single-minded2 (sim2), a Down Syndrome-related transcription factor and homolog of a Drosophila gene (sim) required for LR asymmetric looping of the fly gut. We demonstrate that sim2 functions downstream of LR patterning cues to regulate key cellular properties and behaviors in the left stomach epithelium that drive asymmetric curvature. Our results reveal unexpected convergent cooption of single-minded genes during the evolution of LR asymmetric morphogenesis, and have implications for dose-dependent roles of laterality factors in non-laterality-related birth defects.

scholarly journals Effects of PIN on Osteoblast Differentiation and Matrix Mineralization through Runt-Related Transcription Factor

2020 ◽  
Vol 21 (24) ◽  
pp. 9579
Author(s):  
Kyung-Ran Park ◽  
SooHyun Kim ◽  
MyoungLae Cho ◽  
Sang Wook Kang ◽  
Hyung-Mun Yun
Keyword(s):  
Transcription Factor ◽  
Cell Migration ◽  
Protein Level ◽  
Osteoblast Differentiation ◽  
Signaling Molecules ◽  
Dependent Manner ◽  
Alizarin Red ◽  
Matrix Mineralization ◽  
Related Transcription Factor ◽  
Dose Dependent

Styrax Japonica Sieb. et Zucc. has been used as traditional medicine in inflammatory diseases, and isolated compounds have shown pharmacological activities. Pinoresinol glucoside (PIN) belonging to lignins was isolated from the stem bark of S. Japonica. This study aimed to investigate the biological function and mechanisms of PIN on cell migration, osteoblast differentiation, and matrix mineralization. Herein, we investigated the effects of PIN in MC3T3-E1 pre-osteoblasts, which are widely used for studying osteoblast behavior in in vitro cell systems. At concentrations ranging from 0.1 to 100 μM, PIN had no cell toxicity in pre-osteoblasts. Pre-osteoblasts induced osteoblast differentiation, and the treatment of PIN (10 and 30 μM) promoted the cell migration rate in a dose-dependent manner. At concentrations of 10 and 30 μM, PIN elevated early osteoblast differentiation in a dose-dependent manner, as indicated by increases in alkaline phosphatase (ALP) staining and activity. Subsequently, PIN also increased the formation of mineralized nodules in a dose-dependent manner, as indicated by alizarin red S (ARS) staining, demonstrating positive effects of PIN on late osteoblast differentiation. In addition, PIN induced the mRNA level of BMP2, ALP, and osteocalcin (OCN). PIN also upregulated the protein level of BMP2 and increased canonical BMP2 signaling molecules, the phosphorylation of Smad1/5/8, and the protein level of Runt-related transcription factor 2 (RUNX2). Furthermore, PIN activated non-canonical BMP2 signaling molecules, activated MAP kinases, and increased β-catenin signaling. The findings of this study indicate that PIN has biological roles in osteoblast differentiation and matrix mineralization, and suggest that PIN might have anabolic effects in bone diseases such as osteoporosis and periodontitis.

scholarly journals Limonoid Triterpene, Obacunone Increases Runt-Related Transcription Factor 2 to Promote Osteoblast Differentiation and Function

2021 ◽  
Vol 22 (5) ◽  
pp. 2483
Author(s):  
Kyung-Ran Park ◽  
SooHyun Kim ◽  
MyoungLae Cho ◽  
Hyung-Mun Yun
Keyword(s):  
Transcription Factor ◽  
Osteoblast Differentiation ◽  
Bone Diseases ◽  
Nuclear Accumulation ◽  
Root Bark ◽  
Dependent Manner ◽  
Matrix Mineralization ◽  
Related Transcription Factor ◽  
Anti Inflammatory ◽  
Dose Dependent

Root bark of Dictamnus dasycarpus Turcz. has been widely used as a traditional medicine and is a well-known anti-inflammatory agent. We isolated limonoid triterpene, obacunone (Obac) from the dried root bark of D. dasycarpus. Obac has been reported to exhibit varieties of biological activities including anti-inflammatory, anti-cancer, and anti-oxidant effects. This study aimed to investigate the beneficial effects and biological mechanisms of Obac in osteoblast differentiation and bone matrix mineralization. In the present study, Obac at concentrations ranging from 1 to 100 μM showed no proliferation effects in MC3T3-E1. The treatment of Obac (1 and 10 μM) increased wound healing and migration rates in a dose-dependent manner. Alkaline phosphatase (ALP) staining and activity showed that Obac (1 and 10 μM) enhanced early osteoblast differentiation in a dose-dependent manner. Obac also increased late osteoblast differentiation in a dose-dependent manner, as indicated by the mineralized nodule formation of ARS staining. The effects of Obac on osteoblast differentiation was validated by the levels of mRNAs encoding the bone differentiation markers, including Alp, bone sialoprotein (Bsp), osteopontin (Opn), and osteocalcin (Ocn). Obac increased the expression of bone morphogenetic protein (BMP), and the phosphorylation of smad1/5/8, and the expression of runt-related transcription factor 2 (RUNX2); Obac also inhibited GSK3β and upregulated the protein level of β-catenin in a dose-dependent manner during osteoblast differentiation. Obac-mediated osteoblast differentiation was attenuated by a BMP2 inhibitor, Noggin and a Wnt/β-catenin inhibitor, Dickkopf-1 (Dkk1) with the abolishment of RUNX2 expression and nuclear accumulation by Obac. Taken together, the findings of this study demonstrate that Obac has pharmacological and biological activates to promote osteoblast differentiation and bone mineralization through BMP2, β-catenin, and RUNX2 pathways, and suggest that Obac might be a therapeutic effect for the treatment and prevention of bone diseases such as osteoporosis and periodontitis.

Detection of deleted in malignant brain tumors 1 and runt-related transcription factor 3 gene expressions in bladder carcinoma

2011 ◽  
Vol 39 (4) ◽  
pp. 4691-4695 ◽  
Author(s):  
Yavuz Dodurga ◽  
Çığır Biray Avcı ◽  
N. Lale Satiroglu-Tufan ◽  
Canten Tataroglu ◽  
Zehra Kesen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Brain Tumors ◽  
Bladder Carcinoma ◽  
Gene Expressions ◽  
Malignant Brain Tumors ◽  
Related Transcription Factor ◽  
Transcription Factor 3

scholarly journals Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17β-oestradiol

2017 ◽  
Vol 117 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Youri Jin ◽  
Myoungsook Lee ◽  
Yongsoon Park
Keyword(s):  
Transcription Factor ◽  
Bone Loss ◽  
Protective Efficacy ◽  
Recovery Period ◽  
Serum Levels ◽  
Protective Mechanism ◽  
Beneficial Effects ◽  
Combined Use ◽  
Related Transcription Factor ◽  
Turnover Markers

AbstractOestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1β. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1β and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β.

scholarly journals Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770163 ◽  
Author(s):  
Snigdha Saikia ◽  
Asad Ur Rehman ◽  
Prajjalendra Barooah ◽  
Preeti Sarmah ◽  
Mallika Bhattacharyya ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Transcription Factor ◽  
Promoter Methylation ◽  
Messenger Rna ◽  
Dna Methyltransferase ◽  
Rna Expression ◽  
Betel Nut ◽  
Methylguanine Dna Methyltransferase ◽  
Related Transcription Factor ◽  
Transcription Factor 3

Promoter methylation reflects in the inactivation of different genes like O6-methylguanine-DNA methyltransferase DNA repair gene and runt-related transcription factor 3, a known tumor suppressor gene in various cancers such as esophageal cancer. The promoter methylation was evaluated for O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in CpG, CHH, and CHG context (where H is A, T, or C) by next-generation sequencing. The methylation status was correlated with quantitative messenger RNA expression. In addition, messenger RNA expression was correlated with different risk factors like tobacco, alcohol, betel nut consumption, and smoking habit. CpG methylation of O6-methylguanine-DNA methyltransferase promoter had a positive association in the development of esophageal cancer (p < 0.05), whereas runt-related transcription factor 3 promoter methylation showed no significant association (p = 1.0) to develop esophageal cancer. However, the non-CpG methylation, CHH, and CHG were significantly correlated with O6-methylguanine-DNA methyltransferase (p < 0.05) and runt-related transcription factor 3 (p < 0.05) promoters in the development of esophageal cancer. The number of cytosine converted to thymine (C→T) in O6-methylguanine-DNA methyltransferase promoter showed a significant correlation between cases and controls (p < 0.05), but in runt-related transcription factor 3 no such significant correlation was observed. Besides, messenger RNA expression was found to be significantly correlated with promoter hypermethylation of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in the context of CHG and CHH (p < 0.05). The CpG hypermethylation in O6-methylguanine-DNA methyltransferase showed positive (p < 0.05) association, whereas in runt-related transcription factor 3, it showed contrasting negative association (p = 0.23) with their messenger RNA expression. Tobacco, betel nut consumption, and smoking habits were associated with altered messenger RNA expression of O6-methylguanine-DNA methyltransferase (p < 0.05) and betel nut consumption and smoking habits were associated with runt-related transcription factor 3 (p < 0.05). There was no significant association between messenger RNA expression of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 with alcohol consumption (p = 0.32 and p = 0.15). In conclusion, our results suggest that an aberrant messenger RNA expression may be the outcome of CpG, CHG, and CHH methylation in O6-methylguanine-DNA methyltransferase, whereas outcome of CHG and CHH methylation in runt-related transcription factor 3 promoters along with risk factors such as consumption of tobacco, betel nut, and smoking habits in esophageal cancer from Northeast India.

scholarly journals Leukemia-related transcription factor TEL accelerates differentiation of Friend erythroleukemia cells

Oncogene ◽  
2003 ◽  
Vol 22 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Kazuo Waga ◽  
Yuichi Nakamura ◽  
Kazuhiro Maki ◽  
Honoka Arai ◽  
Tetsuya Yamagata ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Erythroleukemia Cells ◽  
Related Transcription Factor ◽  
Friend Erythroleukemia Cells
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