ArticleThe Journal of clinical investigation2000
Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 390 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
390 citing papers in PubMed, 895 citations in OpenAlex.
- Rhythms of growth: unveiling the mechanobiology behind heart maturation.The Journal of physiology · 2026Review
- Article
- Hyaluronan Underlies the Emergence of Form, Fate, and Function in Human Cardioids.bioRxiv : the preprint server for biology · 2026Article
- Hyaluronan Regulates Vascular Smooth Muscle Cell Osteogenic Differentiation and Vascular Calcification.Biomolecules · 2026Article
- Angiogenesis, Angiogenic Factors, and Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS).International journal of urology : official journal of the Japanese Urological Association · 2026Review
- DNA Methylation and Fetal Programming of Cardiovascular Disease: From Congenital Heart Diseases to Adult Cardiovascular Dysfunction.Reviews in cardiovascular medicine · 2026Review
- Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026Review
- Environmentally dependent developmental induction as a potential driver of heart evolution.The Journal of experimental biology · 2026Review
- BMPR2 affects valve development via ECM-receptor interaction in zebrafish.Frontiers in cell and developmental biology · 2026Article
- Understanding Fascial Tissue on the Molecular Level-How Its Unique Properties Enable Adaptation or Dysfunction.International journal of molecular sciences · 2025Review
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Review
- Article
- Matrix: a complex amalgam of structures and functions in tumor microenvironment.FEBS open bio · 2025Review
- Hyaluronidase-1 mediates postprandial suppression of hepatic gluconeogenesis.Life metabolism · 2025Article
- Procollagen IIA mediates positive feedback control of the mouse cardiogenic transcriptional network.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Hyaluronic Acid in Female Reproductive Health: Tailoring Molecular Weight to Clinical Needs in Obstetric and Gynecological Fields.Pharmaceutics · 2025Review
- Proteoglycans and glycosaminoglycans: critical regulators in angiogenesis, vasculogenesis, and vascularized tissue engineering.Angiogenesis · 2025Review
- Therapeutic Effects of Two Different Molecular Weights of Orally Administered Hyaluronan, Both as Monotherapy and in Combination with Methotrexate in a Rat Model of Arthritis.International journal of molecular sciences · 2025Article
- Activated cardiac fibroblasts are a primary source of high-molecular-weight hyaluronan production.American journal of physiology. Cell physiology · 2025Article
330 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
We identified hyaluronan synthase-2 (Has2) as a likely source of hyaluronan (HA) during embryonic development, and we used gene targeting to study its function in vivo. Has2(-/-) embryos lack HA, exhibit severe cardiac and vascular abnormalities, and die during midgestation (E9.5-10). Heart explants from Has2(-/-) embryos lack the characteristic transformation of cardiac endothelial cells into mesenchyme, an essential developmental event that depends on receptor-mediated intracellular signaling. This defect is reproduced by expression of a dominant-negative Ras in wild-type heart explants, and is reversed in Has2(-/-) explants by gene rescue, by administering exogenous HA, or by expressing activated Ras. Conversely, transformation in Has2(-/-) explants mediated by exogenous HA is inhibited by dominant-negative Ras. Collectively, our results demonstrate the importance of HA in mammalian embryogenesis and the pivotal role of Has2 during mammalian development. They also reveal a previously unrecognized pathway for cell migration and invasion that is HA-dependent and involves Ras activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.