Regulation of hyaluronan biosynthesis and clinical impact of excessive hyaluronan production

Heldin, Paraskevi; Lin, Chun‐Yu; Kolliopoulos, Constantinos; Chen, Yen-Hsu; Skandalis, Spyros S.

doi:10.1016/j.matbio.2018.01.017

Cited by 96 publications

(80 citation statements)

References 175 publications

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“…HA growing chains are extruded onto the cell surface or into the ECM through the plasma membrane and HAS protein complexes [89,90]. The three HAS isoforms share the 50-71% of their amino acid sequences (55% HAS1/HAS2, 57% HAS1/HAS3, 71% HAS2/HAS3) and, indeed, they are all characterized by seven membrane-spanning regions and a central cytoplasmic domain [50,86,89]. However, HAS gene sequences are located on different chromosomes (hCh19-HAS1, hCh8-HAS2, and hCh16-HAS3) [91,92], and the expression and the activity of HAS isoforms are controlled by growth factors, cytokines and other proteins such as kinases in different fashions which appear cell and tissue specific [50,90,93,94].…”

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

“…The three HAS isoforms share the 50-71% of their amino acid sequences (55% HAS1/HAS2, 57% HAS1/HAS3, 71% HAS2/HAS3) and, indeed, they are all characterized by seven membrane-spanning regions and a central cytoplasmic domain [50,86,89]. However, HAS gene sequences are located on different chromosomes (hCh19-HAS1, hCh8-HAS2, and hCh16-HAS3) [91,92], and the expression and the activity of HAS isoforms are controlled by growth factors, cytokines and other proteins such as kinases in different fashions which appear cell and tissue specific [50,90,93,94]. Hence, the three HAS genes may respond differently to transcriptional signals: for example, in human fibroblasts like synoviocytes, transforming growth factor ß upregulates HAS1 expression, but down-regulates HAS3 expression [95].…”

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

“…Dysregulation and misregulation of HAS genes expression results in abnormal production of HA and, therefore, in increased risk of pathological events, altered cell responses to injury, and aberrant biological processes such as malignant transformation and metastasis [47,48,50,100].…”

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

“…Molecular mass and circumstances of synthesis/degradation are the key factors defining HA biological actions [50,51,100]. Indeed, high molecular weight (HMW) and low molecular weight (LMW) hyaluronan can even display opposite effects [51,60], and when they are simultaneously present in a specific tissue, they can exert actions different from the simple sum of those of their separate size-related effects [51].…”

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

“…Indeed, LMW hyaluronan is able to stimulate the production of proinflammatory cytokines, chemokines and growth factors [51], and to promote ECM remodeling [50]. Moreover, LMW HA can also induce tumor progression, exerting its influence on cell [51,116] and provoking ECM remodeling.…”

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

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Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Since its first isolation in 1934, hyaluronic acid (HA) has been studied across a variety of research areas. This unbranched glycosaminoglycan consisting of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid is almost ubiquitary in humans and in other vertebrates. HA is involved in many key processes -including cell signaling, wound reparation, tissue regeneration, morphogenesis, matrix organization and pathobiology-, and has unique physico-chemical properties -such as biocompatibility, biodegradability, mucoadhesivity, hygroscopicity and viscoelasticity. For these reasons, exogenous HA has been investigated as drug delivery system and treatment in cancer, ophthalmology, arthrology, pneumology, rhinology, urology, aesthetic medicine and cosmetic. To improve and customize its properties and applications, HA can be subjected to chemical modifications: conjugation and crosslinking. The present review gives an overview regarding HA, describing its history, physico-chemical, structural and hydrodynamic properties, and biology -occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors. Furthermore, both conventional and recently emerging methods developed for the industrial production of HA and its chemical derivatization are presented. Finally, the medical, pharmaceutical and cosmetic applications of HA and its derivatives are reviewed, reporting examples of HA-based products which currently are on the market or are undergoing further investigations.

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Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

See 3 more Smart Citations

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Functional organization of extracellular hyaluronan, CD44, and RHAMM

Cowman

Turley

2023

Proteoglycan Research

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The integral membrane protein CD44 is constitutively expressed in most tissues, and is the primary cell surface receptor for hyaluronan (HA). HA is the key scaffolding organizer of proteoglycans and receptors in the extracellular matrix. CD44 is expressed as cell type‐specific and context‐specific alternatively spliced isoforms with variable glycosylation and interreceptor interactions. CD44 plays a critical role in the organization and patterning of domains in the cell membrane, achieved through linking the cortical actin cytoskeleton with the pericellular HA matrix. This functional and spatial organization of CD44 and HA maintains a protective and homeostatic cellular microenvironment. Tissue injury and cellular stress result in HA fragmentation and unconventional export of the CD44 coreceptor, RHAMM, which collectively alter the homeostatic organization of CD44/HA. The resulting interplay among HA, HA fragments, CD44 and RHAMM triggers cellular responses such as cell motility that contribute to tissue repair, and disease processes. Here we review current understanding of the structural biology of HA, CD44, and RHAMM, and provide an overview of their known functional organization and patterning at the cell surface. Changes in their surface organization act as sensors for detecting danger, and are critical to the understanding of consequent intracellular signaling and response mechanisms to cellular stress.

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