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MicroRNA-224 Is Involved in Transforming Growth Factor-β-Mediated Mouse Granulosa Cell Proliferation and Granulosa Cell Function by Targeting Smad4

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TLDR
This is the first demonstration that miRNAs can control reproductive functions resulting in promoting TGF-beta1-induced GC proliferation and ovarian estrogen release.
Abstract
Many members of the TGF-beta superfamily are indicated to play important roles in ovarian follicular development, such as affecting granulosa cell function and oocyte maturation. Abnormalities associated with TGF-beta1 signaling transduction could result in female infertility. MicroRNAs (miRNAs), as small noncoding RNAs, were recently found to regulate gene expression at posttranscriptional levels. However, little is known about the role of miRNAs in TGF-beta-mediated granulosa cell proliferation and granulosa cell function. In this study, the miRNA expression profiling was identified from TGF-beta1-treated mouse preantral granulosa cells (GCs), and three miRNAs were found to be significantly up-regulated and 13 miRNAs were down-regulated. Among up-regulated miRNAs, miR-224 was the second most significantly elevated miRNA. This up-regulation was attenuated by treatment of GCs with SB431542 (an inhibitor of TGFbeta superfamily type I receptors, thus blocking phosphorylation of the downstream effectors Smad2/3), indicating that miR-224 expression was regulated by TGF-beta1/Smads pathway. The ectopic expression of miR-224 can enhance TGF-beta1-induced GC proliferation through targeting Smad4. Inhibition of endogenous miR-224 partially suppressed GC proliferation induced by TGF-beta1. In addition, both miR-224 and TGF-beta1 can promote estradiol release from GC, at least in part, through increasing CYP19A1 mRNA levels. This is the first demonstration that miRNAs can control reproductive functions resulting in promoting TGF-beta1-induced GC proliferation and ovarian estrogen release. Such miRNA-mediated effects could be potentially used for regulation of reproductive processes or for treatment of reproductive disorders.

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Journal ArticleDOI

TGF-β Signaling from Receptors to Smads.

TL;DR: This review introduces some basic components of the TGF-β signaling pathways and their actions, and discusses posttranslational modifications and modulatory partners that modify the outcome of the signaling and contribute to its context-dependence, including small noncoding RNAs.
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Molecular control of oogenesis.

TL;DR: Recent knowledge on the molecular aspects of oogenesis and oocyte maturation, and the crucial role of cumulus-cell interactions are summarized, highlighting the valuable contribution of experimental evidences obtained in animal models.
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MicroRNA biogenesis: Regulating the Regulators

TL;DR: The basic steps of miRNA biogenesis are reviewed and the various factors that control miRNA transcription, processing, and stability in animal cells are described.
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MicroRNA-21 Integrates Pathogenic Signaling to Control Pulmonary Hypertension Results of a Network Bioinformatics Approach

TL;DR: In this article, microRNA-21 (miR-21) is predicted as a PH-modifying microRNA, regulating targets integral to bone morphogenetic protein (BMP) and Rho/Rho-kinase signaling as well as functional pathways associated with hypoxia, inflammation, and genetic haploinsufficiency of BMP receptor type 2.
References
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Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method

TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
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MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets

TL;DR: In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of the gene set.
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The functions of animal microRNAs

TL;DR: Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
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TGF-beta signal transduction.

TL;DR: The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms and mutations in these pathways are the cause of various forms of human cancer and developmental disorders.
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