Size‐dependent hyaluronate degradation by cultured cells

McGuire, Paul; Castellot, John J.; Orkin, Roslyn W.

doi:10.1002/jcp.1041330210

Cited by 69 publications

(47 citation statements)

References 68 publications

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“…Previous work has indicated that cells prefer to take up hyaluronan of low molecular weight (McGuire et al 1987). Our results further these findings and suggest that the size of the hyaluronan may also influence its distribution intracellularly.…”

Section: Intracellular Hyaluronansupporting

confidence: 89%

“…wt. 1000 kD) was partially fragmented before incubation with the cells by brief digestion with Streptomyces hyaluronidase, 100 mU/ml, for 10 min at 37C or by brief sonication as previously described (McGuire et al 1987). As determined by comparison on agarose gels, the sonicated material had a molecular weight of 300 kD and the enzyme-digested material was less than 50 kD.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Intracellular Hyaluronan in Arterial Smooth Muscle Cells: Association with Microtubules, RHAMM, and the Mitotic Spindle

Evanko¹,

Parks

Wight³

2004

J Histochem Cytochem.

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S U M M A R YAlthough considered a pericellular matrix component, hyaluronan was recently localized in the cytoplasm and nucleus of proliferating cells, supporting earlier reports that hyaluronan was present in locations such as the nucleus, rough endoplasmic reticulum, and caveolae. This suggests that it can play roles both inside and outside the cell. Hyaluronan metabolism is coupled to mitosis and cell motility, but it is not clear if intracellular hyaluronan associates with cytoskeletal elements or plays a structural role. Here we report the distribution of intracellular hyaluronan, microtubules, and RHAMM in arterial smooth muscle cells in vitro. The general distribution of intracellular hyaluronan more closely resembled microtubule staining rather than actin filaments. Hyaluronan was abundant in the perinuclear microtubule-rich areas and was present in lysosomes, other vesicular structures, and the nucleolus. Partially fragmented fluorescein-hyaluronan was preferentially translocated to the perinuclear area compared with high-molecular-weight hyaluronan. In the mitotic spindle, hyaluronan colocalized with tubulin and with the hyaladherin RHAMM, a cell surface receptor and microtubule-associated protein that interacts with dynein and maintains spindle pole stability. Internalized fluorescein-hyaluronan was also seen at the spindle. Following telophase, an abundance of hyaluronan near the midbody microtubules at the cleavage furrow was also noted. In permeabilized cells, fluorescein-hyaluronan bound to RHAMM-associated microtubules. These findings suggest novel functions for hyaluronan in cellular physiology.

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Section: Intracellular Hyaluronansupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Intracellular Hyaluronan in Arterial Smooth Muscle Cells: Association with Microtubules, RHAMM, and the Mitotic Spindle

Evanko¹,

Parks

Wight³

2004

J Histochem Cytochem.

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“…2E). It was previously suggested that HA originates from the pericellular material that is degraded intracellularly (30,31). Our data suggest that hESCs are able to uptake and degrade HA and thereby remodel HA gels, a feature necessary for cell survival and migration.…”

Section: Resultssupporting

confidence: 57%

Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells

Gerecht

Burdick

Ferreira

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

612

445

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Control of self-renewal and differentiation of human ES cells (hESCs)remains a challenge. This is largely due to the use of culture systems that involve poorly defined animal products and do not mimic the normal developmental milieu. Routine protocols involve the propagation of hESCs on mouse fibroblast or human feeder layers, enzymatic cell removal, and spontaneous differentiation in cultures of embryoid bodies, and each of these steps involves significant variability of culture conditions. We report that a completely synthetic hydrogel matrix can support (i) long-term self-renewal of hESCs in the presence of conditioned medium from mouse embryonic fibroblast feeder layers, and (ii) direct cell differentiation. Hyaluronic acid (HA) hydrogels were selected because of the role of HA in early development and feeder layer cultures of hESCs and the controllability of hydrogel architecture, mechanics, and degradation. When encapsulated in 3D HA hydrogels (but not within other hydrogels or in monolayer cultures on HA), hESCs maintained their undifferentiated state, preserved their normal karyotype, and maintained their full differentiation capacity as indicated by embryoid body formation. Differentiation could be induced within the same hydrogel by simply altering soluble factors. We therefore propose that HA hydrogels, with their developmentally relevant composition and tunable physical properties, provide a unique microenvironment for the selfrenewal and differentiation of hESCs.scaffolds ͉ three-dimensional cultures ͉ vasculogenesis

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“…At a time when synthesis is increased, the most plausible explanation for the relatively low total cell surface hyaluronan content is reduction in the receptor-bound pool, perhaps because of a more rapid uptake into the cell. The smaller hyaluronan chains (found in the medium) may be readily endocytosed (rather than remaining resident) after binding to the receptors (41), and cause a backlog in the degradation pathway. Enhanced hyaluronidase activity at the cell surface (42), along with CD44, could enlarge the initial uptake compartment with intermediate size hyaluronan (28), and also reduce the average size of the hyaluronan released into medium.…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte Growth Factor Stimulates Migration and Hyaluronan Synthesis in the Epidermis by Activation of Keratinocyte Hyaluronan Synthases 2 and 3

Karvinen

Pasonen‐Seppänen

Hyttinen

et al. 2003

Journal of Biological Chemistry

156

125

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Keratinocyte growth factor (KGF) activates keratinocyte migration and stimulates wound healing. Hyaluronan, an extracellular matrix glycosaminoglycan that accumulates in wounded epidermis, is known to promote cell migration, suggesting that increased synthesis of hyaluronan might be associated with the KGF response in keratinocytes. Treatment of monolayer cultures of rat epidermal keratinocytes led to an elongated and lifted cell shape, increased filopodial protrusions, enhanced cell migration, accumulation of intermediate size hyaluronan in the culture medium and within keratinocytes, and a rapid increase of hyaluronan synthase 2 (Has2) mRNA, suggesting a direct influence on this gene. In stratified, organotypic cultures of the same cell line, both Has2 and Has3 with the hyaluronan receptor CD44 were up-regulated and hyaluronan accumulated in the epidermis, the spinous cell layer in particular. At the same time the expression of the early differentiation marker keratin 10 was inhibited, whereas filaggrin expression and epidermal permeability were less affected. The data indicate that Has2 and Has3 belong to the targets of KGF in keratinocytes, and support the idea that enhanced hyaluronan synthesis acts an effector for the migratory response of keratinocytes in wound healing, whereas it may delay keratinocyte terminal differentiation.

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Size‐dependent hyaluronate degradation by cultured cells

Cited by 69 publications

References 68 publications

Intracellular Hyaluronan in Arterial Smooth Muscle Cells: Association with Microtubules, RHAMM, and the Mitotic Spindle

Intracellular Hyaluronan in Arterial Smooth Muscle Cells: Association with Microtubules, RHAMM, and the Mitotic Spindle

Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells

Keratinocyte Growth Factor Stimulates Migration and Hyaluronan Synthesis in the Epidermis by Activation of Keratinocyte Hyaluronan Synthases 2 and 3

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