Li, T.-S. | bioRxiv Science

bioRxiv2022

eccDB: a comprehensive repository for eccDNA-mediated chromatin contacts in multi-species

The role of extrachromosomal circular DNA (eccDNA) has been highlighted. More recently, eccDNA-chromosome interactions were identified, suggesting a potential role of eccDNA in transcriptional regulation. Several databases currently provide valuable resources for the study of eccDNAs. However, these databases are primarily focused on Human eccDNAs and do not provide analysis of eccDNA-chromosome interaction and eccDNA gene expression in different tissues. Herein, to further integrate available resources for eccDNA data across multiple species, we developed the eccDB database. The current version of eccDB has collected a total of 1,317,182 eccDNAs in 424 samples from four species (homo sapiens, mus musculus, saccharomyces cerevisiae, and arabidopsis thaliana). eccDB provides regulatory and epigenetic information on eccDNA, including typical enhancers, super-enhancers, transcription factors, DNA methylation positions, risk SNPs, expression quantitative trait locus, chromatin accessibility regions, and chromHMM states. In particular, eccDB provides eccDNAs intrachromosomal and interchromosomal interaction analysis to predict the transcriptional regulatory functions of eccDNA. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of an eccDNA among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNA. eccDB is freely available at http://www.xiejjlab.bio/eccDB

bioinformatics↗

bioRxiv2020

Increased ketohexokinase-A governs fructose-induced podocyte hypertrophy by IL-6/STAT3 signaling activation

Glomerular hypertrophy is crucial for podocyte damage and proteinuria. Our previous study showed that fructose induced podocyte injury. However, the molecular mechanism underlying podocyte hypertrophy under fructose is unclear. We observed that fructose significantly initiated the hypertrophy in rat glomeruli and cultured differentiated human podocytes (HPCs). Consistently, it induced inflammatory response with the down-regulation of zinc-finger protein tristetraprolin (TTP) and the activation of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling in these animal and cell models. Subsequently, high-expression of miR-92a-3p and its target protein cyclin-dependent kinase inhibitor p57 (P57) down-regulation, representing the abnormal proliferation and apoptosis, were observed in vivo and in vitro. Moreover, fructose increased ketohexokinase-A (KHK-A) in rat glomeruli and HPCs. Animal-free recombinant human IL-6, maslinic acid and TTP siRNA were used to manifest that fructose may decrease TTP to activate IL-6/STAT3 signaling in podocyte overproliferation and apoptosis, causing podocyte hypertrophy. KHK-A siRNA transfection further demonstrated that the inactivation of IL-6/STAT3 to relieve podocyte hypertrophy mediated by inhibiting KHK-A to increase TTP may be a novel strategy for fructose-associated podocyte injury and proteinuria. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/424520v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@243c32org.highwire.dtl.DTLVardef@ec1784org.highwire.dtl.DTLVardef@1fbe0b6org.highwire.dtl.DTLVardef@15dd5f3_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗