scholarly journals Exploring the Roles of Fecundity-related mRNAs and Long Non-coding RNAs in the Adrenal Glands of Small-tailed Han Sheep

2020 ◽  
Author(s):  
Qing Xia ◽  
Qiuling Li ◽  
Shangquan Gan ◽  
Xiaofei Guo ◽  
Xiaosheng Zhang ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Gene Expressions ◽  
Non Coding Rnas

Abstract Background Long non-coding RNAs (lncRNAs) can play important roles in uterine and ovarian functions. However, little researches have been done on the role of lncRNAs in the adrenal gland of sheep. Herein, RNA sequencing was used to compare and analyze gene expressions in adrenal tissues between FecB ++ (WW) and FecB BB (MM) sheep in the follicular and luteal phases and key lncRNAs and genes associated with reproduction were identified. Results In MM sheep, 38 lncRNAs and 545 mRNAs were differentially expressed in the adrenal gland between the luteal and follicular phases; In WW sheep, 30 differentially expressed lncRNAs and 210 mRNAs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that differentially expressed lncRNAs and their target genes are mainly involved in the circadian rhythm, the mitogen activated protein kinase, thyroid, ovarian steroidogenesis and transforming growth factor beta signaling pathways. Key lncRNAs can regulate reproduction by modulating genes involved in these signaling pathways and biological processes. Specifically, XLOC_254761 , XLOC_357966 , 105614839 and XLOC_212877 targeting CREB1 , PER3 , SMAD1 and TGFBR2 , respectively, appear to play key regulatory roles. Conclusion These results broaden our understanding of lncRNAs in adrenal gland of sheep and provide new insights into the molecular mechanisms underlying sheep reproduction.

scholarly journals Exploring the Roles of Fecundity-related Long Non-coding RNAs and mRNAs in the Adrenal Glands of Small-tailed Han Sheep

2020 ◽  
Author(s):  
Qing Xia ◽  
Qiuling Li ◽  
Shangquan Gan ◽  
Xiaofei Guo ◽  
Xiaosheng Zhang ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Gene Expressions ◽  
Non Coding Rnas

Abstract Background: Long non-coding RNAs (lncRNAs) can play important roles in uterine and ovarian functions. However, little researches have been done on the role of lncRNAs in the adrenal gland of sheep. Herein, RNA sequencing was used to compare and analyze gene expressions in adrenal tissues between follicular phases and luteal phases in FecBBB (MM) and FecB++ (WW) sheep, respectively, and differentially expressed lncRNAs and genes associated with reproduction were identified.Results: In MM sheep, 38 lncRNAs and 545 mRNAs were differentially expressed in the adrenal gland between the luteal and follicular phases; In WW sheep, 513 differentially expressed lncRNAs and 2481 mRNAs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that differentially expressed lncRNAs and their target genes are mainly involved in the circadian rhythm, the mitogen activated protein kinase, thyroid, ovarian steroidogenesis and transforming growth factor beta signaling pathways. Differentially expressed lncRNAs can regulate reproduction by modulating genes involved in these signaling pathways and biological processes. Specifically, XLOC_254761, XLOC_357966, 105614839 and XLOC_212877 targeting CREB1, PER3, SMAD1 and TGFBR2, respectively, appear to play key regulatory roles. Conclusion: These results broaden our understanding of lncRNAs in adrenal gland of sheep and provide new insights into the molecular mechanisms underlying sheep reproduction.

scholarly journals Exploring the Roles of Fecundity-related mRNAs and Long Non-coding RNAs in the Adrenal Glands of Small-tailed Han Sheep

2019 ◽  
Author(s):  
Qing Xia ◽  
Qiuling Li ◽  
Shangquan Gan ◽  
Xiaofei Guo ◽  
Xiaosheng Zhang ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Gene Expressions ◽  
Non Coding Rnas

Abstract Background Long non-coding RNAs (lncRNAs) can play important roles in uterine and ovarian functions. However, little researches have been done on the role of lncRNAs in the adrenal gland of sheep. Herein, RNA sequencing was used to compare and analyze gene expressions in adrenal tissues between FecB ++ (WW) and FecB BB (MM) sheep in the follicular and luteal phases and key lncRNAs and genes associated with reproduction were identified.Results In MM sheep, 38 lncRNAs and 545 mRNAs were differentially expressed in the adrenal gland between the luteal and follicular phases; In WW sheep, 30 differentially expressed lncRNAs and 210 mRNAs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that differentially expressed lncRNAs and their target genes are mainly involved in the circadian rhythm, the mitogen activated protein kinase, thyroid, ovarian steroidogenesis and transforming growth factor beta signaling pathways. Key lncRNAs can regulate reproduction by modulating genes involved in these signaling pathways and biological processes. Specifically, XLOC_254761 , XLOC_357966 , 105614839 and XLOC_212877 targeting CREB1 , PER3 , SMAD1 and TGFBR2 , respectively, appear to play key regulatory roles.Conclusion These results broaden our understanding of lncRNAs in adrenal gland of sheep and provide new insights into the molecular mechanisms underlying sheep reproduction.

scholarly journals Exploring the Roles of Fecundity-related Long Non-coding RNAs and mRNAs in the Adrenal Gland of Small-tailed Han Sheep

2020 ◽  
Author(s):  
Qing Xia ◽  
Qiuling Li ◽  
Shangquan Gan ◽  
Xiaofei Guo ◽  
Xiaosheng Zhang ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Gene Expressions ◽  
Non Coding Rnas

Abstract Background: Long non-coding RNAs (lncRNAs) can play important roles in uterine and ovarian functions. However, little researches have been done on the role of lncRNAs in the adrenal gland of sheep. Herein, RNA sequencing was used to compare and analyze gene expressions in adrenal tissue between follicular phase and luteal phase in FecBBB (MM) and FecB++ (WW) sheep, respectively, and differentially expressed lncRNAs and genes associated with reproduction were identified.Results: In MM sheep, 38 lncRNAs and 545 mRNAs were differentially expressed in the adrenal gland between the luteal and follicular phases; In WW sheep, 513 differentially expressed lncRNAs and 2481 mRNAs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that differentially expressed lncRNAs and their target genes are mainly involved in the circadian rhythm, the mitogen activated protein kinase, thyroid, ovarian steroidogenesis and transforming growth factor beta signaling pathways. Differentially expressed lncRNAs can regulate reproduction by modulating genes involved in these signaling pathways and biological processes. Specifically, XLOC_254761, XLOC_357966, 105614839 and XLOC_212877 targeting CREB1, PER3, SMAD1 and TGFBR2, respectively, appear to play key regulatory roles. Conclusion: These results broaden our understanding of lncRNAs in adrenal gland of sheep and provide new insights into the molecular mechanisms underlying sheep reproduction.

scholarly journals The TGFβ-induced phosphorylation and activation of p38 mitogen-activated protein kinase is mediated by MAP3K4 and MAP3K10 but not TAK1

Open Biology ◽  
2013 ◽  
Vol 3 (6) ◽  
pp. 130067 ◽  
Author(s):  
Gopal P. Sapkota
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Phosphorylation ◽  
Mesenchymal Transition ◽  
Mitogen Activated Protein

The signalling pathways downstream of the transforming growth factor beta (TGFβ) family of cytokines play critical roles in all aspects of cellular homeostasis. The phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) has been implicated in TGFβ-induced epithelial-to-mesenchymal transition and apoptosis. The precise molecular mechanisms by which TGFβ cytokines induce the phosphorylation and activation of p38 MAPK are unclear. In this study, I demonstrate that TGFβ-activated kinase 1 (TAK1/MAP3K7) does not play a role in the TGFβ-induced phosphorylation and activation of p38 MAPK in MEFs and HaCaT keratinocytes. Instead, RNAi -mediated depletion of MAP3K4 and MAP3K10 results in the inhibition of the TGFβ-induced p38 MAPK phosphorylation. Furthermore, the depletion of MAP3K10 from cells homozygously knocked-in with a catalytically inactive mutant of MAP3K4 completely abolishes the TGFβ-induced phosphorylation of p38 MAPK, implying that among MAP3Ks, MAP3K4 and MAP3K10 are sufficient for mediating the TGFβ-induced activation of p38 MAPK.

scholarly journals RNA-Seq Profiling of Circular RNAs During Development of Hindgut in Rat Embryos With Ethylenethiourea-Induced Anorectal Malformations

2021 ◽  
Vol 12 ◽  
Author(s):  
Si Ying Li ◽  
Chen Yi Wang ◽  
Yun Xia Xiao ◽  
Xiao Bing Tang ◽  
Zheng Wei Yuan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Anorectal Malformations ◽  
Normal Group ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Circular Rnas ◽  
Rna Seq ◽  
Pregnant Rats

Anorectal malformations (ARMs) are among the most common congenital terminal digestive tract malformations. Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, play roles in the development of the digestive system; however, their contributions to the pathogenesis of ARMs are not well-established. In this study, we explored the mechanism underlying ethylenethiourea (ETU)-induced ARMs by profiling circRNA expression via RNA-seq and constructing a regulatory circRNA-miRNA-mRNA network. Nine pregnant rats were gavage-fed a single dose of 125 mg/kg 1% ETU (ARM group) on gestational day 10 (GD10), and another 9 pregnant rats received a similar dose of saline (normal group) as a control. Embryos were obtained by cesarean section on the key time-points of anorectal development (GD14, GD15, and GD16). Hindgut samples isolated from the fetuses were evaluated by high-throughput sequencing and differentially expressed circRNAs were validated by reverse transcription-quantitative polymerase chain reaction, agarose gel electrophoresis, and Sanger cloning and sequencing. A total of 18295 circRNAs were identified in the normal and ARM groups. Based on the 425 differentially expressed circRNAs (|Fc| > 2, p < 0.05), circRNA-miRNA and miRNA-mRNA pairs were predicted using miREAP, miRanda, and TargetScan. A total of 55 circRNAs (14 up- and 41 downregulated in the ARM group compared to the normal group) were predicted to bind to 195 miRNAs and 947 mRNAs. Competing endogenous RNA networks and a Kyoto Encyclopedia of Genes and Genomes analysis revealed that novel_circ_001042 had the greatest connectivity and was closely related to ARM-associated signaling pathways, such as the Wingless Type MMTV integration site family, mitogen-activated protein kinase, and transforming growth factor-β pathways. These results provide original insight into the roles of circRNAs in ARMs and provide a valuable resource for further analyses of molecular mechanisms and signaling networks.

scholarly journals Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Fanglong Wu ◽  
Jin Yang ◽  
Junjiang Liu ◽  
Ye Wang ◽  
Jingtian Mu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Matrix Remodeling ◽  
Cancer Associated Fibroblasts

AbstractTo flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence and progression because of their versatile roles in extracellular matrix remodeling, maintenance of stemness, blood vessel formation, modulation of tumor metabolism, immune response, and promotion of cancer cell proliferation, migration, invasion, and therapeutic resistance. CAFs are highly heterogeneous stromal cells and their crosstalk with cancer cells is mediated by a complex and intricate signaling network consisting of transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers and activators of transcription, epidermal growth factor receptor, Hippo, and nuclear factor kappa-light-chain-enhancer of activated B cells, etc., signaling pathways. These signals in CAFs exhibit their own special characteristics during the cancer progression and have the potential to be targeted for anticancer therapy. Therefore, a comprehensive understanding of these signaling cascades in interactions between cancer cells and CAFs is necessary to fully realize the pivotal roles of CAFs in cancers. Herein, in this review, we will summarize the enormous amounts of findings on the signals mediating crosstalk of CAFs with cancer cells and its related targets or trials. Further, we hypothesize three potential targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential target perturbation, and crosstalk-directed signaling targets, paving the way for CAF-directed or host cell-directed antitumor therapy.

scholarly journals Construction and Analysis of a ceRNA Network in Cardiac Fibroblast During Fibrosis Based on in vivo and in vitro Data

2021 ◽  
Vol 11 ◽  
Author(s):  
Qing-Yuan Gao ◽  
Hai-Feng Zhang ◽  
Zhi-Teng Chen ◽  
Yue-Wei Li ◽  
Shao-Hua Wang ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Target Genes ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Single Gene ◽  
Cardiac Fibroblast ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Cerna Network

AimsActivation of cardiac fibroblasts (CF) is crucial to cardiac fibrosis. We constructed a cardiac fibroblast-related competing endogenous RNA (ceRNA) network. Potential functions related to fibrosis of “hub genes” in this ceRNA network were explored.Materials and MethodsThe Gene Expression Omnibus database was searched for eligible datasets. Differentially expressed messenger (m)RNA (DE-mRNA) and long non-coding (lnc)RNA (DE-lncRNA) were identified. microRNA was predicted and validated. A predicted ceRNA network was constructed and visualized by Cytoscape, and ceRNA crosstalk was validated. A Single Gene Set Enrichment Analysis (SGSEA) was done, and the Comparative Toxicogenomics Database (CTD) was employed to analyze the most closely associated pathways and diseases of DE-mRNA in the ceRNA network. The functions of DE-mRNA and DE-lncRNA in the ceRNA network were validated by small interfering (si)RNA depletion.ResultsThe GSE97358 and GSE116250 datasets (which described differentially expressed genes in human cardiac fibroblasts and failing ventricles, respectively) were used for analyses. Four-hundred-and-twenty DE-mRNA and 39 DE-lncRNA, and 369 DE-mRNA and 93 DE-lncRNA were identified, respectively, in the GSE97358 and GSE116250 datasets. Most of the genes were related to signal transduction, cytokine activity, and cell proliferation. Thirteen DE-mRNA with the same expression tendency were overlapped in the two datasets. Twenty-three candidate microRNAs were predicted and the expression of 11 were different. Only two DE-lncRNA were paired to any one of 11 microRNA. Finally, two mRNA [ADAM metallopeptidase domain 19, (ADAM19) and transforming growth factor beta induced, (TGFBI)], three microRNA (miR-9-5p, miR-124-3p, and miR-153-3p) and two lncRNA (LINC00511 and SNHG15) constituted our ceRNA network. siRNA against LINC00511 increased miR-124-3p and miR-9-5p expression, and decreased ADAM19 and TGFBI expression, whereas siRNA against SNHG15 increased miR-153-3p and decreased ADAM19 expression. ADAM19 and TGFBI were closely related to the TGF-β1 pathway and cardiac fibrosis, as shown by SGSEA and CTD, respectively. Depletion of two mRNA or two lncRNA could alleviate CF activation.ConclusionsThe CF-specific ceRNA network, including two lncRNA, three miRNA, and two mRNA, played a crucial role during cardiac fibrosis, which provided potential target genes in this field.

scholarly journals Identification and Characterization of Long Non-Coding RNA in Tomato Roots under Salt Stress

2021 ◽  
Author(s):  
Ning Li ◽  
Zhongyu Wang ◽  
Baike Wang ◽  
Juan Wang ◽  
Ruiqiang Xu ◽  
...  
Keyword(s):  
Salt Stress ◽  
Salt Tolerance ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Differentially Expressed ◽  
Vegetable Crops ◽  
Tomato Roots ◽  
Non Coding Rnas

As one of the most important vegetable crops in the world, the production of tomatoes was restricted by salt stress. Therefore, it is of great interest to analyze the salt stress tolerance genes. As the non-coding RNAs (ncRNAs) with a length of more than 200 nucleotides, long non-coding RNAs (lncRNAs) lack the ability of protein-coding, but they can play crucial roles in plant development and response to abiotic stresses by regulating gene expression. Nevertheless, there are few studies on the roles of salt-induced lncRNAs in tomatoes. Therefore, we selected wild tomato Solanum pennellii (S. pennellii) and cultivated tomato M82 to be materials. By high-throughput sequencing, 1044 putative lncRNAs were identified here. Among them, 154 and 137 lncRNAs were differentially expressed in M82 and S. pennellii, respectively. Through functional analysis of target genes of differentially expressed lncRNAs (DE-lncRNAs), some genes were found to respond positively to salt stress by participating in Abscisic Acid (ABA) signaling pathway, brassinosteroid (BR) signaling pathway, ethylene (ETH) signaling pathway and anti-oxidation process. We also construct a salt-induced lncRNA-mRNA co-expression network to dissect the putative mechanisms of high salt tolerance in S. pennellii. We analyze the function of salt-induced lncRNAs in tomato roots at the genome-wide levels for the first time. These results will contribute to understanding the molecular mechanisms of salt tolerance in tomatoes from the perspective of lncRNAs.

scholarly journals Astragaloside IV ameliorates early diabetic nephropathy by inhibition of MEK1/2-ERK1/2-RSK2 signaling in streptozotocin-induced diabetic mice

2018 ◽  
Vol 46 (7) ◽  
pp. 2883-2897 ◽  
Author(s):  
Gaofeng Song ◽  
Pengxun Han ◽  
Huili Sun ◽  
Mumin Shao ◽  
Xuewen Yu ◽  
...  
Keyword(s):  
Body Weight ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Fasting Blood Glucose ◽  
Mitogen Activated Protein Kinase ◽  
Diabetic Mice ◽  
Astragaloside Iv ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Ribosomal S6 Kinase

Objective The aim of this study was to investigate the renoprotective effects and molecular mechanisms of astragaloside IV (AS-IV) in streptozotocin (STZ)-induced diabetic mice. Methods Male C57BL/6 mice were injected intraperitoneally with STZ at 200 mg/kg body weight. AS-IV was administered for 8 consecutive weeks, beginning 1 week after STZ injection. Body weight, 24-hour urinary albumin excretion, and fasting blood glucose were measured. Kidney tissues were examined by histopathological analyses. Total levels and phosphorylation of mitogen-activated protein kinase 1/2 (MEK1/2), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and ribosomal S6 kinase 2 (RSK2) were determined by Western blotting analysis. Results AS-IV treatment significantly reduced albuminuria and serum creatinine levels, ameliorated mesangial matrix expansion and greater foot process width, and decreased the levels of urinary N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, and transforming growth factor-beta 1 in STZ-induced diabetic mice. AS-IV also inhibited renal cortical phosphorylation of MEK1/2, ERK1/2 and RSK2. Conclusion Our results suggest that AS-IV attenuates renal injury in STZ-induced diabetic mice. This effect might be partially associated with inhibition of the activation of the MEK1/2-ERK1/2-RSK2 signaling pathway.

scholarly journals MicroRNAs—The Heart of Post-Myocardial Infarction Remodeling

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1675
Author(s):  
Liana Maries ◽  
Cătălin Marian ◽  
Raluca Sosdean ◽  
Flavia Goanta ◽  
Ioan Ovidiu Sirbu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Left Ventricular

Myocardial infarction (MI) is one of the most frequent cardiac emergencies, with significant potential for mortality. One of the major challenges of the post-MI healing response is that replacement fibrosis could lead to left ventricular remodeling (LVR) and heart failure (HF). This process involves canonical and non-canonical transforming growth factor-beta (TGF-β) signaling pathways translating into an intricate activation of cardiac fibroblasts and disproportionate collagen synthesis. Accumulating evidence has indicated that microRNAs (miRNAs) significantly contribute to the modulation of these signaling pathways. This review summarizes the recent updates regarding the molecular mechanisms underlying the role of the over 30 miRNAs involved in post-MI LVR. In addition, we compare the contradictory roles of several multifunctional miRNAs and highlight their potential use in pressure overload and ischemia-induced fibrosis. Finally, we discuss their attractive role as prognostic biomarkers for HF, highlighting the most relevant human trials involving these miRNAs.

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