ArticleThe Journal of biological chemistry2011
The human hyaluronan synthase 2 (HAS2) gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.Molecular psychiatry · 2021Pooled it
- Effects of U62631.5 on short-chain fatty acid receptor 41(GPR41) and the related intestinal bacterium Butyricicoccus pullicaecorum after fecal bacterial transplantation in nonalcoholic fatty liver disease.BMC microbiology · 2026Article
- Understanding Fascial Tissue on the Molecular Level-How Its Unique Properties Enable Adaptation or Dysfunction.International journal of molecular sciences · 2025Review
- Bone quality relies on hyaluronan synthesis - Insights from mice with complete knockout of hyaluronan synthase expression.Matrix biology plus · 2024Article
- Natural antisense transcripts as versatile regulators of gene expression.Nature reviews. Genetics · 2024Review
- Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.Cardiovascular research · 2023Article
- Effects of Hyaluronan on Breast Cancer Aggressiveness.Cancers · 2023Review
- The Upregulation of HAS2-AS1 Relates to the Granulosa Cell Dysfunction by Repressing TGF-β Signaling and Upregulating HAS2.Molecular and cellular biology · 2022Article
- Hyaluronan, a double-edged sword in kidney diseases.Pediatric nephrology (Berlin, Germany) · 2022Review
- Article
- Long Non-coding Antisense RNA DDIT4-AS1 Regulates Meningitic Escherichia coli-Induced Neuroinflammation by Promoting DDIT4 mRNA Stability.Molecular neurobiology · 2022Article
- Analysis of Human Hyaluronan Synthase Gene Transcriptional Regulation and Downstream Hyaluronan Cell Surface Receptor Mobility in Myofibroblast Differentiation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.Research (Washington, D.C.) · 2022Review
- The role of the multifaceted long non-coding RNAs: A nuclear-cytosolic interplay to regulate hyaluronan metabolism.Matrix biology plus · 2021Article
- Inflammation, Extracellular Matrix Remodeling, and Proteostasis in Tumor Microenvironment.International journal of molecular sciences · 2021Review
- The Transcription Factor C/EBPβ Promotes HFL-1 Cell Migration, Proliferation, and Inflammation by Activating lncRNA HAS2-AS1 in Hypoxia.Frontiers in cell and developmental biology · 2021Article
- Cell Energy Metabolism and Hyaluronan Synthesis.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Review
- LncRNA FAM83H-AS1 promotes oesophageal squamous cell carcinoma progression via miR-10a-5p/Girdin axis.Journal of cellular and molecular medicine · 2020Article
- Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2-AS1.The Journal of biological chemistry · 2020Article
- Molecular determinants of mesenchymal cell activation in fibroproliferative diseases.Cellular and molecular life sciences : CMLS · 2019Review
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10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant expression of the human hyaluronan synthase 2 (HAS2) gene has been implicated in the pathology of malignancy, pulmonary arterial hypertension, osteoarthritis, asthma, thyroid dysfunction, and large organ fibrosis. Renal fibrosis is associated with increased cortical synthesis of hyaluronan (HA), an extracellular matrix glycosaminoglycan, and we have shown that HA is a correlate of interstitial fibrosis in vivo. Our previous in vitro data have suggested that both HAS2 transcriptional induction and subsequent HAS2-driven HA synthesis may contribute to kidney fibrosis via phenotypic modulation of the renal proximal tubular epithelial cell (PTC). Post-transcriptional regulation of HAS2 mRNA synthesis by the natural antisense RNA HAS2-AS1 has recently been described in osteosarcoma cells, but the antisense transcript was not detected in kidney. In this study, PTC stimulation with IL-1β or TGF-β1 induced coordinated temporal profiles of HAS2-AS1 and HAS2 transcription. Constitutive activity of the putative HAS2-AS1 promoter was demonstrated, and transcription factor-binding sequence motifs were identified. Knockdown of Sp1/Sp3 expression by siRNA blunted IL-1β induction of both HAS2-AS1 and HAS2, and Smad2/Smad3 knockdown similarly attenuated TGF-β1 stimulation. Inhibition of IL-1β-stimulated HAS2-AS1 RNA induction using HAS2-AS1-specific siRNAs also suppressed up-regulation of HAS2 mRNA transcription. The thermodynamic feasibility of HAS2-AS1/HAS2 heterodimer formation was demonstrated in silico, and locus-specific cytoplasmic double-stranded RNA was detected in vitro. In summary, our data show that transcriptional induction of HAS2-AS1 and HAS2 occurs simultaneously in PTCs and suggest that transcription of the antisense RNA stabilizes or augments HAS2 mRNA expression in these cells via RNA/mRNA heteroduplex formation.
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