Characterization of the collagen of human hypertrophic and normal scars

Bailey, Allen J.; Bazin, S; Sims, Trevor J.; Lous, Mady Le; Nicolétis, C; Delaunay, A

doi:10.1016/0005-2795(75)90106-3

Cited by 261 publications

(107 citation statements)

References 17 publications

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“…Perhaps some of the hormonal changes associated with diabetes, such as increased insulin and growth hormone levels, stimulate epithelial cells to revert to a pattern of fetal collagen production, with increased lysyl hydroxylase activity and increased type III collagen production. Although it is possible that the alterations in DHLNL observed in diabetic skin could be attributed to an increase in type III collagen, there is evidence that, at least in hypertrophic scarring, increases in DHLNL are associated with type I collagen as well as with type III collagen (29).…”

Section: Discussionmentioning

confidence: 99%

Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus.

Buckingham

Reiser²

1990

J. Clin. Invest.

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IntroductionMany abnormalities in collagen have been reported in insulindependent diabetes mellitus, some or all of which have been attributed to increased cross-linking. Although recent work has focused on the role of glucose-derived collagen cross-links in the pathogenesis of diabetic complications, relatively few studies have investigated the role of lysyl oxidase-dependent (LOX) cross-links. In the present study, LOX cross-links and nonenzymatic glycosylation were quantified in skin collagen from diabetic subjects. There was an increase in the difunctional cross-link dihydroxylysinonorleucine (DHLNL) as well as in one of its trifunctional maturation products, hydroxypyridinium. All other LOX crosslinks were normal. Nonenzymatic glycosylation was increased in diabetic skin collagen, and this increase was correlated with increases in DHLNL (P < 0.001).The biochemical results were examined for correlations with clinical data from the same subjects. Increases in DHLNL content were associated with duration of diabetes (P < 0.003), glycohemoglobin levels (P < 0.001), hand contractures (P < 0.05), skin changes (P < 0.005), and microalbuminuria (P < 0.01). In nondiabetic subjects age was not correlated with collagen cross-link content with the exception that his-HLNL increased with age (r = 0.79, P < 0.02). In diabetic subjects, PA levels decreased with age (r = 0.51, P < 0.02). With increased duration of diabetes, DHLNL content was increased (r = 0.55, P < 0.003) and OHP was increased (r = 0.59, P < 0.01), whereas PA levels were decreased (r = -0.48, P < 0.04) (Fig. 5). Nonenzymatic glycosylation of collagen was also increased with increased duration of diabetes (hex-lys, r = 0.47, P < 0.02; hex-hyl, r = 039, P < 0.05). We conclude that: (a) lysyl oxidase-dependent cross-linking is increased in skin collagen in diabetes and (b) that these changes in skin collagen are correlated with duration of diabetes, glycemic control, and long-term complications. (J. Clin. Invest. 1990.

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Section: Discussionmentioning

confidence: 99%

Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus.

Buckingham

Reiser²

1990

J. Clin. Invest.

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“…Therefore, during the early phase of soft tissue repair, there is an alteration in the type 1II:type I collagen ratio to that which is typically present in embryonic connective tissue [7]. It has been suggested that the lower tensile strength of scar tissue during the early healing period is related to the high proportion of type III collagen [2,3]. In animal models of ligament healing, scar tissue has been shown to contain up to 40% type 111 collagen 14 weeks after injury [7].…”

Section: Introductionmentioning

confidence: 99%

“…In certain pathologic conditions, the type 1II:type I collagen ratio is altered. For example, while normal scar tissue has a low type 1II:type I collagen ratio, hypertrophied scar is similar to embryonic muscle tissue with a high type 1II:type I collagen ratio [3]. There is great interest in understanding the regulation of these processes and these findings have prompted a number of investigators to study the use of exogenous growth factors to potentially control scar formation and improve recovery following ligament injury [14,16,18].…”

Section: Introductionmentioning

confidence: 99%

Analysis of changes in mRNA levels of myoblast‐ and fibroblast‐derived gene products in healing skeletal muscle using quantitative reverse transcription‐polymerase chain reaction

Best

Shehadeh

Leverson

et al. 2001

Journal Orthopaedic Research

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Changes in expression of type I l l al-collagen and myosin I1 heavy chains were characterized in rabbit skeletal muscle following single stretch injury using quantitative reverse transcription-polymerase chain reaction. Collagen 111 expression was highly elevated in the injured leg compared with the control limb both at the myotendinous junction and in the distal muscle belly. While upregulation of collagen I11 expression at the myotendinous junction was maximal on day 1. collagen 111 expression in the distal muscle belly was unchanged on day 1 but highly elevated by day 3. Over the initial 7-day period, there was on average a 94% increase in collagen Ill expression at the myotendinous junction and a 41% increase in the distal muscle belly. On the other hand, there was little difference, in fact, slightly less expression of myosin I1 isoforms, in the injured leg compared with the control side. Immunohistochemical analysis of injured muscle showed significant collagen 111 deposition at the myotendinous junction beginning at day 3 post-injury and still evident by day 14. Focal deposits of type I and 111 collagen were first apparent in the distal muscle belly by day 3 and striking by day 7. Taken together, the data suggest the formation of connective tissue scar at the injury site and the absence of significant muscle regeneration following muscle stretch. Furthermore, microinjuries distant to the primary site of injury may result in more general muscle fibrosis and scarring. 0 3001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

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“…[12][13][14] Furthermore, collagen cross-links in healing skin wounds and in sclerotic skin of hypertrophic scars, lipodermatosclerosis (LDS) and scleroderma are characterized by a shift from lysine-aldehyde derived cross-links primarily observed in adult skin to hydroxylysine-aldehyde derived cross-links characteristic for fetal skin. [15][16][17] Also, for several non-collagenous matrix proteins an increase of embryo-fetal proteins was reported in wound healing and sclerosis: The splice variant EDA of fibronectin, a 440 kDa adhesive matrix glycoprotein characterized by an additional type III repeat between repeats 11 and 12, is expressed in the developing embryo, but is barely detectable in adult skin. EDA was also found in wound healing and sclerosis and together with TGF-b is thought to be important for the generation of myofibroblasts.…”

mentioning

confidence: 96%

Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: potential alteration of cell attachment and storage of TGF-β

Brinckmann

Hunzelmann

Kahle

et al. 2010

Laboratory Investigation

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Wound healing and sclerosis are characterized by an increase of extracellular matrix proteins, which are characteristically expressed in the embryo-fetal period. We analyzed the expression of fibrillin-2, which is typically found in embryonic tissues, but only scarcely in adult skin. In wound healing and sclerotic skin diseases such as lipodermatosclerosis and scleroderma, a marked increase of fibrillin-2 expression was found by immunohistology. Double labelling of fibrillin-2 and tenascin-C, which is also expressed in wound healing and sclerosis, showed co-localization of both proteins. Solid-phase and slot blot-overlay assays showed a dose-dependent binding of the recombinant N-terminal half of fibrillin-2 (rFBN2-N) to tenascin-C. Real-time PCR showed an increase of the fibrillin-2 gene expression in cell culture triggered by typical mediators for fibroblast activation such as serum, IL-4, and TGF-b. By contrast, prolonged hypoxia is not associated with changes in fibrillin-2 expression. Tenascin-C is an anti-adhesive substrate for fibroblasts, whereas fibrillin-2 stimulates cell attachment. Attachment assays using mixed substrates showed decreased cell attachment when tenascin-C and rFBN2-N were coated together, compared with the attachment to rFBN2-N alone. Fibrillins are involved in storage and activation of TGF-b. Immunohistology with an antibody against the latency-associated peptide (LAP (TGF-b1)) showed a marked increase of inactive LAP-bound TGF-b1 in wound healing and sclerotic skin whereas normal skin showed only a weak expression. Double immunofluorescence confirmed a partial colocalization of both proteins. In conclusion, we show that a stimulation of the fibrillin-2 expression is a characteristic feature of fibroblasts present in wound healing and sclerosis, which may be involved in the alteration of cell attachment and storage of inactive TGF-b in the matrix.

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Characterization of the collagen of human hypertrophic and normal scars

Cited by 261 publications

References 17 publications

Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus.

Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus.

Analysis of changes in mRNA levels of myoblast‐ and fibroblast‐derived gene products in healing skeletal muscle using quantitative reverse transcription‐polymerase chain reaction

Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: potential alteration of cell attachment and storage of TGF-β

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