Adenoviral expression of a transforming growth factor-beta1 antisense mRNA is effective in preventing liver fibrosis in bile-duct ligated rats. | LitMetric
Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, Aachen, D-52074, Germany.
Published: October 2003
AI Article Synopsis
Article Abstract
Background: Transforming growth factor-beta (TGF-beta) is a key mediator in establishing liver fibrosis. Therefore, TGF-beta as a causative agent may serve as a primary target for antifibrotic gene therapy approaches. We have previously shown that the adenoviral delivery of a transgene constitutively expressing a TGF-beta1 antisense mRNA blocks TGF-beta synthesis in culture-activated hepatic stellate cells and effectively abolishes ongoing fibrogenesis in vitro.
Methods: Ligature of the common bile duct was used to induce liver fibrosis in rats. The effect of the TGF-beta1 antisense on fibrogenesis was analyzed in this model of liver injury.
Results: In the present study, we demonstrate that the adenoviral vector directs the synthesis of mRNA quantities that are approximately 8000-fold more abundant than endogenous TGF-beta1 mRNA. In experimentally injured rat livers induced by ligature of the common bile duct, a model for persistent fibrogenesis and cirrhosis, administration of the adenoviral vector abrogates TGF-beta-enhanced production of collagen and alpha-smooth muscle actin. Furthermore, the number of cells positive for alpha-smooth muscle actin resulting from active recruitment of activated hepatic stellate cells around the bile ductular structures was significantly reduced in animals after application of Ad5-CMV-AS-TGF-beta1. However, the observed elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and bilirubin induced in this obstructive liver injury model were not significantly altered in the presence of the TGF-beta antagonist.
Conclusion: Taken together, our data provides in vivo evidence that the delivery of TGF-beta1 antisense mRNA specifically abolishes the diverse effects of direct TGF-beta function in ongoing liver fibrogenesis. Therefore, we conclude that the expressed transgene is therapeutically useful for inhibition of TGF-beta effects in diverse applications, ranging from clarification of TGF-beta function in the course of liver injury to the development of novel gene therapeutic approaches.
Objective: Long non-coding RNA (lncRNA) has been playing an increasingly significant role in neuropathic pain (NP). This study aimed to investigate the clinical significance and mechanism of LncRNA ZNFX1 antisense RNA 1 (ZFAS1) in NP.
Methods: 92 patients with NP and healthy controls were enrolled, and a rat NP model was constructed by chronic constrictive injury (CCI).
Background: Previous studies in mouse, and zebrafish embryos show strong expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 ( in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.
Methods: Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies.
Biogenesis of circular RNA usually involves a backsplicing reaction where the downstream donor site is ligated to the upstream acceptor site by the spliceosome. For this reaction to occur, it is hypothesized that these sites must be in proximity. Inverted repeat sequences, such as Alu elements, in the upstream and downstream introns are predicted to base-pair and represent one mechanism for inducing proximity.
RNA-seq and its 5'-enrichment methods for prokaryotes have enabled the precise identification of transcription start sites (TSSs), improving gene expression analysis. Computational methods are applied to these data to identify TSSs and classify them based on proximal annotated genes. While some TSSs cannot be classified at all (orphan TSSs), other TSSs are found on the reverse strand of known genes (antisense TSSs) but are not associated with the direct transcription of any known gene.
State Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China. Electronic address:
Nitric oxide (NO) is a crucial signaling molecule that regulates a wide range of metabolic pathways in different strata of organisms. In plants, nitrate reductase (NR) is a key enzyme for NO biosynthesis. There are two NR-encoding genes in Arabidopsis, NIA1 and NIA2, which are precisely regulated and expressed in a tissue-specific manner.
