Fetal response to injury in the rabbit

Krummel, Thomas M.; Nelson, Jeffrey M.; Diegelmann, Robert F.; Lindblad, William J.; Salzberg, A.M.; Greenfield, Lazar J.; Cohen, I. Kelman

doi:10.1016/s0022-3468(87)80117-3

Cited by 186 publications

(55 citation statements)

References 20 publications

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“…2 We hypothesized that HA would inhibit collagen contraction by smooth muscle cells and adventitial fibroblasts on the basis of reports implicating HA in scarless fetal wound healing. 5,[25][26][27] Early fetal skin has a high HA content, and incisions heal by regeneration without fibrosis or scar. 5,25 HA content falls as the fetus matures, and wounds then heal by scarring with granulation tissue, contraction, and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…5,[25][26][27] Early fetal skin has a high HA content, and incisions heal by regeneration without fibrosis or scar. 5,25 HA content falls as the fetus matures, and wounds then heal by scarring with granulation tissue, contraction, and fibrosis. 11 Exogenous HA can shift the phenotype of late fetal wounds from scarring to regeneration, suggesting a transition linked mechanistically to loss of HA.…”

Section: Discussionmentioning

confidence: 99%

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Hyaluronan Enhances Contraction of Collagen by Smooth Muscle Cells and Adventitial Fibroblasts

Travis

Hughes

Wong

et al. 2001

Circulation Research

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Abstract-Remodeling contributes to restenosis when cells shrink the artery wall at sites of injury. This may be analogous to wound healing, where tissue remodeling achieves wound contraction. Hyaluronan (HA) is prominent in wound matrix and inhibits fetal scarring. HA is also produced in the artery wall after angioplasty, where it may inhibit constrictive remodeling. This hypothesis was tested in vitro using a model of matrix contraction. Primate aortic smooth muscle cells and adventitial fibroblasts were seeded into collagen I gels containing increasing amounts of HA (0% to 50%, wt/wt). Both cell types reduced the diameter of collagen alone Ϸ65% at 18 hours. HA significantly increased gel contraction (diameter in mm: 0% HA, 7.7Ϯ0.9; 2%, 7.1Ϯ0.7; 10%, 6.7Ϯ0.5; 50%, 5.6Ϯ0.9; PϽ0.05 for Ն10%), cell spreading and telopodia, and pericellular accumulation of collagen fibrils. These effects were mediated in part by cellular HA binding, because an antibody against CD44 receptors blocked pericellular collagen accumulation and enhanced gel contraction without altering cell shape. The role of CD44 was specific, because inhibiting receptor for hyaluronic acid-mediated motility (RHAMM) had no effect. Blocking ␤ 1 -integrins completely inhibited contraction of collagen, but gels containing HA required CD44 and ␤ 1 -integrin blockade for complete inhibition. Enhanced collagen reorganization and contraction were not attributable to increased collagenase activity, because the metalloproteinase inhibitor batimastat had no effect. In summary, HA enhanced collagen reorganization by the cell types most likely to mediate constrictive remodeling after angioplasty. These effects were CD44-dependent, thus providing a potential target for therapies to prevent constrictive remodeling and restenosis. (Circ Res. 2001;88:77-83.)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hyaluronan Enhances Contraction of Collagen by Smooth Muscle Cells and Adventitial Fibroblasts

Travis

Hughes

Wong

et al. 2001

Circulation Research

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“…If the unique character of the "ends" persists after fusion, their exposure by proteases at the time of injury might provide a suitable old site to which newly formed segments might associate. The unusual healing properties of fetal and newborn tissues might be explained, in part, by the presence of more frequent or less modified segments (24). If rearrangements at the tissue level are more possible with short segments, then injury to a young tissue presents the cells with less difficulty in repair.…”

Section: Discussionmentioning

confidence: 99%

Collagen fibrillogenesis in situ: fibril segments are intermediates in matrix assembly.

Birk

Zycband

Winkelmann

et al. 1989

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

151

127

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The assembly of discontinuous fibril segments and bundles was studied in 14-day chicken embryo tendons by using serial sections, transmission electron microscopy, and computer-assisted image reconstruction. Fibril segments were first found in extracytoplasmic channels, the sites of their polymerization; they also were found within fibril bundles. Single fibril segments were followed over their entire length in consecutive sections, and their lengths ranged from 7 to 15 atm. Structural differences in the ends of the fibril segments were identified, suggesting that the amino/carboxyl polarity of the fibril segment is reflected in its architecture. Our data indicate that fibril segments are precursors in collagen fibril formation, and we suggest that postdepositional fusion of fibril segments may be an important process in tendon development and growth.Collagen is the major protein in tissues such as tendon, cornea, bone, and skin, and at least 12 different molecular forms have been isolated from vertebrates (1, 2). Type I collagen is the most abundant and plays a major role in structure stabilization. One level of organization of type I collagen molecules is into fibrils, which are long, filamentous, quasi-crystalline aggregates whose biochemical and molecular attributes have been described in detail (3). Fibrils are organized into bundles, which are themselves organized into macroaggregates such as the nearly orthogonal layers in bone and cornea, the less regular layers in dermis, and the nearly uniaxial arrangement in tendons and ligaments.The self-assembly of type I collagen has been studied extensively in vitro, and many inferences about in situ assembly have been drawn from these studies (4). Collagen fibril formation in situ is a multistep process involving intracellular as well as extracellular compartments defined by the fibroblast (5). Fibroblasts exert control over collagen fibril formation in a number of ways, including control of the stoichiometry of different matrix gene products during synthesis and subsequent packaging for secretion (5, 6), vectorial discharge of macromolecules (5-7), and formation of extracellular compartments for matrix assembly (8-12). These cellular influences are well illustrated in the developing tendon, where fibril segment polymerization occurs within deep channels in the fibroblast surface, and fibril bundle formation occurs within a more peripheral extracytoplasmic compartment defined by single or adjacent fibroblasts (11,12). This compartmentalization of the extracellular space presumably permits the fibroblast to partition the fibril segments, fibrils, fibril bundles, macroaggregates, and the processing enzymes necessary for the postdepositional modification of the polymers.However, these observations do not explain the mechanism whereby, long, seemingly endless collagen fibrils with mechanical integrity are assembled during development, growth, and repair. In the present study, we demonstrate that 14-day chicken embryo tendon fibroblasts produce discontinuous fi...

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“…In contrast to adult (postnatal) wound healing, fetal skin wounds heal rapidly with minimal inflammation and no scar formation (Burrington 1971;Krummel et al 1987;Siebert et al 1990). Multiple studies have pointed out the biochemical, physiological and mechanical differences (reviews by Yannas 2005;Wilgus 2007;Hantash et al 2008;Buchanan et al 2009) observed between fetal and adult skin wound healing, but as yet the critical factors determining the disparity in healing outcome have yet to be identified.…”

Section: Introductionmentioning

confidence: 99%

Cloning and expression of rabbit CCT subunits eta and beta in healing cutaneous wounds

Satish

Johnson

Abdulally

et al. 2010

Cell Stress and Chaperones

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We have previously identified the CCT subunit eta as specifically reduced in healing fetal skin wounds by differential display, and observed that this reduction is not seen with any other CCT subunit. We now report the cloning and characterization of the cDNAs for rabbit CCT-eta and its closest evolutionary homolog, CCT-beta. Quantitative examination of CCT-eta and -beta message expression in healing fetal and adult wounds at 12 h post-injury confirms that CCT-eta mRNA is decreased in fetal wound tissues, but actually elevated in adult wound tissues. CCT-beta mRNA, in contrast, remains unchanged in both fetal and adult wound tissues. CCT-eta mRNA remains persistently elevated in healing adult wounds for 28 days following injury, whereas CCT-beta mRNA remains invariant throughout. CCT-eta protein is similarly increased, whereas CCT-beta protein remains unchanged. -smooth muscle actin ( -SMA), a recognized substrate of CCT known to be important in integumentary wound healing, was also measured over the course of wound healing, and both mRNA and protein levels were elevated throughout the 28 days.

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Fetal response to injury in the rabbit

Cited by 186 publications

References 20 publications

Hyaluronan Enhances Contraction of Collagen by Smooth Muscle Cells and Adventitial Fibroblasts

Hyaluronan Enhances Contraction of Collagen by Smooth Muscle Cells and Adventitial Fibroblasts

Collagen fibrillogenesis in situ: fibril segments are intermediates in matrix assembly.

Cloning and expression of rabbit CCT subunits eta and beta in healing cutaneous wounds

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