Browsing by Author "Wu, Jianguo"

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    H19 potentiates let-7 family expression through reducing PTBP1 binding to their precursors in cholestasis
    (Springer Nature, 2019-02-18) Zhang, Li; Yang, Zhihong; Huang, Wendong; Wu, Jianguo; Medicine, School of Medicine
    Cholestasis induces the hepatic long non-coding RNA H19, which promotes the progression of cholestatic liver fibrosis. However, microRNAs that are dysregulated by H19 during cholestasis remain elusive. Using miRNA-sequencing analysis followed by qPCR validation, we identified marked upregulation of eight members of the let-7 family in cholestatic livers by bile duct ligation (BDL) and H19 overexpression. In particular, the expression of let-7a-1/7d/7f-1 was highly induced in H19-BDL livers but decreased in H19KO-BDL livers. Interestingly, H19 decreased the nuclear let-7 precursors as well as the primary transcripts of let-7a-1/7d/7f-1 levels in BDL mouse livers. Bioinformatics, RNA pull-down, and RNA immunoprecipitation (RIP) assays revealed that the crucial RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), an H19 interaction partner, interacted with the precursors of let-7a-1 and let-7d and suppressed their maturation. Both PTBP1 and let-7 expression was differentially regulated by different bile acid species in hepatocyte and cholangiocyte cells. Further, H19 negatively regulated PTBP1's mRNA and protein levels but did not affect its subcellular distribution in BDL mouse livers. Moreover, we found that H19 restrained but PTBP1 facilitated the bioavailability of let-7 miRNAs to their targets. Taken together, this study revealed for the first time that H19 promoted let-7 expression by decreasing PTBP1's expression level and its binding to the let-7 precursors in cholestasis.
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    Impacts of Climate Change on Tibetan Lakes: Patterns and Processes
    (MDPI, 2018-02-26) Mao, Dehua; Wang, Zongming; Yang, Hong; Li, Huiying; Thompson, Julian R.; Li, Lin; Song, Kaishan; Chen, Bin; Gao, Hongkai; Wu, Jianguo; Earth Sciences, School of Science
    High-altitude inland-drainage lakes on the Tibetan Plateau (TP), the earth’s third pole, are very sensitive to climate change. Tibetan lakes are important natural resources with important religious, historical, and cultural significance. However, the spatial patterns and processes controlling the impacts of climate and associated changes on Tibetan lakes are largely unknown. This study used long time series and multi-temporal Landsat imagery to map the patterns of Tibetan lakes and glaciers in 1977, 1990, 2000, and 2014, and further to assess the spatiotemporal changes of lakes and glaciers in 17 TP watersheds between 1977 and 2014. Spatially variable changes in lake and glacier area as well as climatic factors were analyzed. We identified four modes of lake change in response to climate and associated changes. Lake expansion was predominantly attributed to increased precipitation and glacier melting, whereas lake shrinkage was a main consequence of a drier climate or permafrost degradation. These findings shed new light on the impacts of recent environmental changes on Tibetan lakes. They suggest that protecting these high-altitude lakes in the face of further environmental change will require spatially variable policies and management measures.
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    Impacts of Climate Change on Tibetan Lakes: Patterns and Processes
    (MDPI, 2018-02-26) Mao, Dehua; Wang, Zongming; Yang, Hong; Li, Huiying; Thompson, Julian; Li, Lin; Song, Kaishan; Chen, Bin; Gao, Hongkai; Wu, Jianguo; Earth Sciences, School of Science
    High-altitude inland-drainage lakes on the Tibetan Plateau (TP), the earth’s third pole, are very sensitive to climate change. Tibetan lakes are important natural resources with important religious, historical, and cultural significance. However, the spatial patterns and processes controlling the impacts of climate and associated changes on Tibetan lakes are largely unknown. This study used long time series and multi-temporal Landsat imagery to map the patterns of Tibetan lakes and glaciers in 1977, 1990, 2000, and 2014, and further to assess the spatiotemporal changes of lakes and glaciers in 17 TP watersheds between 1977 and 2014. Spatially variable changes in lake and glacier area as well as climatic factors were analyzed. We identified four modes of lake change in response to climate and associated changes. Lake expansion was predominantly attributed to increased precipitation and glacier melting, whereas lake shrinkage was a main consequence of a drier climate or permafrost degradation. These findings shed new light on the impacts of recent environmental changes on Tibetan lakes. They suggest that protecting these high-altitude lakes in the face of further environmental change will require spatially variable policies and management measures.
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    Long Non-coding RNA in Liver Metabolism and Disease: Current Status
    (Elsevier, 2017-09) Zhao, Yulan; Wu, Jianguo; Liangpunsakul, Suthat; Wang, Li; Medicine, School of Medicine
    Long non-coding RNAs (lncRNAs) are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames (with rare exceptions). Herein, we highlight emerging evidence demonstrating that lncRNAs are critical regulators of liver metabolic function and diseases. We summarize current knowledges about dysregulated lncRNAs and outline the underlying molecular mechanisms by which lncRNAs control hepatic lipid ad glucose metabolism, as well as cholestatic liver disease. lncLSTR, Lnc18q22.2, SRA, HULC, MALAT1, lncLGR, MEG3, and H19, lncHR1, lnc-HC, APOA1-AS, DYNLRB2-2, and LeXis are included in the discussion.
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    Non-coding RNA crosstalk with nuclear receptors in liver disease
    (Elsevier, 2021-05) Wu, Jianguo; Nagy, Laura E.; Liangpunsakul, Suthat; Wang, Li; Medicine, School of Medicine
    The dysregulation of nuclear receptors (NRs) underlies the pathogenesis of a variety of liver disorders. Non-coding RNAs (ncRNAs) are defined as RNA molecules transcribed from DNA but not translated into proteins. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two types of ncRNAs that have been extensively studied for regulating gene expression during diverse cellular processes. NRs as therapeutic targets in liver disease have been exemplified by the successful application of their pharmacological ligands in clinics. MiRNA-based reagents or drugs are emerging as flagship products in clinical trials. Advancing our understanding of the crosstalk between NRs and ncRNAs is critical to the development of diagnostic and therapeutic strategies. This review summarizes recent findings on the reciprocal regulation between NRs and ncRNAs (mainly on miRNAs and lncRNAs) and their implication in liver pathophysiology, which might be informative to the translational medicine of targeting NRs and ncRNAs in liver disease.