Person: Wang, Da-Zhi
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Wang
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Da-Zhi
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Wang, Da-Zhi
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Publication Noncoding RNAs, Emerging Regulators of Skeletal Muscle Development and Diseases(Hindawi Publishing Corporation, 2015) Nie, Mao; Deng, Zhong-Liang; Liu, Jianming; Wang, Da-ZhiA healthy and independent life requires skeletal muscles to maintain optimal function throughout the lifespan, which is in turn dependent on efficient activation of processes that regulate muscle development, homeostasis, and metabolism. Thus, identifying mechanisms that modulate these processes is of crucial priority. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have emerged as a class of previously unrecognized transcripts whose importance in a wide range of biological processes and human disease is only starting to be appreciated. In this review, we summarize the roles of recently identified miRNAs and lncRNAs during skeletal muscle development and pathophysiology. We also discuss several molecular mechanisms of these noncoding RNAs. Undoubtedly, further systematic understanding of these noncoding RNAs' functions and mechanisms will not only greatly expand our knowledge of basic skeletal muscle biology, but also significantly facilitate the development of therapies for various muscle diseases, such as muscular dystrophies, cachexia, and sarcopenia.Publication microRNAs in cardiac regeneration and cardiovascular disease(2013) Wu, GengZe; Huang, Zhan-Peng; Wang, Da-ZhimicroRNAs (miRNAs) are a class of small non-coding RNAs, which have been shown important to a wide range of biological process by post-transcriptionally regulating the expression of protein-coding genes. miRNAs have been demonstrated essential to normal cardiac development and function. Recently, numerous studies indicate miRNAs are involved in cardiac regeneration and cardiac disease, including cardiac hypertrophy, myocardial infarction and cardiac arrhythmia. These observations suggest miRNAs play important roles in cardiology. In this review, we summarize the recent progress of studying miRNAs in cardiac regeneration and cardiac disease. We also discuss the diagnostic and therapeutic potential of miRNAs in heart disease.Publication Non-Coding RNAs Including miRNAs and lncRNAs in Cardiovascular Biology and Disease(MDPI, 2014) Kataoka, Masaharu; Wang, Da-ZhiIt has been recognized for decades that proteins, which are encoded by our genome and produced via transcription and translation steps, are building blocks that play vital roles in almost all biological processes. Mutations identified in many protein-coding genes are linked to various human diseases. However, this “protein-centered” dogma has been challenged in recent years with the discovery that the majority of our genome is “non-coding” yet transcribed. Non-coding RNA has become the focus of “next generation” biology. Here, we review the emerging field of non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and their role in cardiovascular function and disease.Publication Trbp regulates heart function through miRNA-mediated Sox6 repression(2015) Ding, Jian; Chen, Jinghai; Wang, Yanqun; Kataoka, Masaharu; Ma, Lixin; Zhou, Pingzhu; Hu, Xiaoyun; Lin, Zhiqiang; Nie, Mao; Deng, Zhong-Liang; Pu, William; Wang, Da-ZhiCardiomyopathy is associated with altered expression of genes encoding contractile proteins. Here we show that Trbp (Tarbp2), an RNA binding protein, is required for normal heart function. Cardiac-specific inactivation of Trbp (TrbpcKO) caused progressive cardiomyopathy and lethal heart failure. Trbp loss of function resulted in upregulation of Sox6, repression of genes encoding normal cardiac slow-twitch myofiber proteins, and pathologically increased expression of skeletal fast-twitch myofiber genes. Remarkably, knockdown of Sox6 fully rescued the Trbp mutant phenotype, whereas Sox6 overexpression phenocopied the TrbpcKO phenotype. Trbp inactivation was mechanistically linked to Sox6 upregulation through altered processing of miR-208a, which is a direct inhibitor of Sox6. Transgenic overexpression of miR-208a sufficiently repressed Sox6, restored the balance of fast- and slow- twitch myofiber gene expression, and rescued cardiac function in TrbpcKO mice. Together, our studies reveal a novel Trbp-mediated microRNA processing mechanism in regulating a linear genetic cascade essential for normal heart function.Publication The Histone Methyltransferase Set7/9 Promotes Myoblast Differentiation and Myofibril Assembly(The Rockefeller University Press, 2011) Tao, Yazhong; Neppl, Ronald; Huang, Zhan-Peng; Chen, Jianfu; Tang, Ru-Hang; Cao, Ru; Zhang, Yi; Jin, Suk-Won; Wang, Da-ZhiThe molecular events that modulate chromatin structure during skeletal muscle differentiation are still poorly understood. We report in this paper that expression of the H3-K4 histone methyltransferase Set7 is increased when myoblasts differentiate into myotubes and is required for skeletal muscle development, expression of muscle contractile proteins, and myofibril assembly. Knockdown of Set7 or expression of a dominant-negative Set7 mutant impairs skeletal muscle differentiation, accompanied by a decrease in levels of histone monomethylation (H3-K4me1). Set7 directly interacts with MyoD to enhance expression of muscle differentiation genes. Expression of myocyte enhancer factor 2 and genes encoding contractile proteins is decreased in Set7 knockdown myocytes. Furthermore, we demonstrate that Set7 also activates muscle gene expression by precluding Suv39h1-mediated H3-K9 methylation on the promoters of myogenic differentiation genes. Together, our experiments define a biological function for Set7 in muscle differentiation and provide a molecular mechanism by which Set7 modulates myogenic transcription factors during muscle differentiation.Publication MicroRNA-1 and MicroRNA-206 Regulate Skeletal Muscle Satellite Cell Proliferation and Differentiation by Repressing Pax7(The Rockefeller University Press, 2010) Chen, Jian-Fu; Tao, Yazhong; Li, Juan; Deng, Zhongliang; Yan, Zhen; Xiao, Xiao; Wang, Da-ZhiSkeletal muscle satellite cells are adult stem cells responsible for postnatal skeletal muscle growth and regeneration. Paired-box transcription factor Pax7 plays a central role in satellite cell survival, self-renewal, and proliferation. However, how Pax7 is regulated during the transition from proliferating satellite cells to differentiating myogenic progenitor cells is largely unknown. In this study, we find that miR-1 and miR-206 are sharply up-regulated during satellite cell differentiation and down-regulated after muscle injury. We show that miR-1 and miR-206 facilitate satellite cell differentiation by restricting their proliferative potential. We identify Pax7 as one of the direct regulatory targets of miR-1 and miR-206. Inhibition of miR-1 and miR-206 substantially enhances satellite cell proliferation and increases Pax7 protein level in vivo. Conversely, sustained Pax7 expression as a result of the loss of miR-1 and miR-206 repression elements at its 3′ untranslated region significantly inhibits myoblast differentiation. Therefore, our experiments suggest that microRNAs participate in a regulatory circuit that allows rapid gene program transitions from proliferation to differentiation.Publication Transgenic Overexpression of miR-133a in Skeletal Muscle(BioMed Central, 2011) Deng, Zhongliang; Chen, Jian-Fu; Wang, Da-ZhiBackground: MicroRNAs (miRNAs) are a class of non-coding regulatory RNAs of ~22 nucleotides in length. miRNAs regulate gene expression post-transcriptionally, primarily by associating with the 3' untranslated region (UTR) of their regulatory target mRNAs. Recent work has begun to reveal roles for miRNAs in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. Many miRNAs are expressed in cardiac and skeletal muscle, and dysregulated miRNA expression has been correlated with muscle-related disorders. We have previously reported that the expression of muscle-specific miR-1 and miR-133 is induced during skeletal muscle differentiation and miR-1 and miR-133 play central regulatory roles in myoblast proliferation and differentiation in vitro. Methods: In this study, we measured the expression of miRNAs in the skeletal muscle of mdx mice, an animal model for human muscular dystrophy. We also generated transgenic mice to overexpress miR-133a in skeletal muscle. Results: We examined the expression of miRNAs in the skeletal muscle of mdx mice. We found that the expression of muscle miRNAs, including miR-1a, miR-133a and miR-206, was up-regulated in the skeletal muscle of mdx mice. In order to further investigate the function of miR-133a in skeletal muscle in vivo, we have created several independent transgenic founder lines. Surprisingly, skeletal muscle development and function appear to be unaffected in miR-133a transgenic mice. Conclusions: Our results indicate that miR-133a is dispensable for the normal development and function of skeletal muscle.