Altered expression of hyaluronan synthase and hyaluronidase <scp>mRNA</scp> may affect hyaluronic acid distribution in keloid disease compared with normal skin

Sidgwick, Gary P; Iqbal, Syed Amir; Bayat, Ardeshir

doi:10.1111/exd.12147

Cited by 24 publications

(12 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HAS and HYAL activities are also reduced in keloids, supporting the earlier observations . Hypertrophic scars also have decreased HA deposition, particularly in the papillary dermis, but intermediate between that of normal scars and that of keloids …”

Section: Other Aspects Of Hyaluronan Metabolism In Wound Healingsupporting

confidence: 85%

Hyaluronan in wound healing: Rediscovering a major player

Aya

Stern

2014

Wound Repair Regeneration

252

221

View full text Add to dashboard Cite

Wound healing involves a series of carefully modulated steps, from initial injury and blood clot to the final reconstituted tissue or scar. A dynamic reciprocity exists throughout between the wound, blood elements, extracellular matrix, and cells that participate in healing. Multiple cytokines and signal transduction pathways regulate these reactions. A major component throughout most of the process is hyaluronan, a straight-chain carbohydrate extracellular matrix polymer. Hyaluronan occurs in multiple forms, chain length being the only distinguishing characteristic between them. Levels of hyaluronan in its high-molecular-weight form are prominent in the earliest stages of wound repair. Progressively more fragmented forms occur in a manner not previously appreciated. We outline here steps in the wound healing cascade in which hyaluronan participates, as well as providing a review of its metabolism. Although described by necessity in a series of quantum steps, the healing process is constituted by a smooth continuum of overlapping reactions. The prevalence of hyaluronan in the wound (initially termed "hexosamine-containing mucopolysaccharide"), particularly in its early stages, was pointed out over half a century ago by the Harvard surgeon J. Engelbert Dunphy. It appears we are now returning to where we started.

show abstract

Section: Other Aspects Of Hyaluronan Metabolism In Wound Healingsupporting

confidence: 85%

Hyaluronan in wound healing: Rediscovering a major player

Aya

Stern

2014

Wound Repair Regeneration

252

221

View full text Add to dashboard Cite

show abstract

“…We found that a gradation in increasing epidermal thickness correlated with the degree of severity of the scar: epidermal-thickness keloid > hypertrophic scar > normotrophic scar > normal skin. In the literature, the keloid epidermis has been described as both appearing morphologically normal 1,2,26,33 and having increased thickness, 14,[34][35][36][37][38] while some found a thicker epidermis in both abnormal scars, 31,39,40 and yet others considered a thicker epidermis to be an inconsistent finding. 28,41 However, to date we have not found a publication comparing and measuring the epidermal thickness of sufficiently matured scars (≥ 1 year old) of the entire scar spectrum in a standardized, quantifiable manner.…”

Section: Discussionmentioning

confidence: 99%

Increased epidermal thickness and abnormal epidermal differentiation in keloid scars

et al. 2016

View full text Add to dashboard Cite

SummaryBackground The pathogenesis underlying keloid formation is still poorly understood. Research has focused mostly on dermal abnormalities, while the epidermis has not yet been studied. Objectives To identify differences within the epidermis of mature keloid scars compared with normal skin and mature normotrophic and hypertrophic scars. Methods Rete ridge formation and epidermal thickness were evaluated in tissue sections. Epidermal proliferation was assessed using immunohistochemistry (Ki67, keratins 6, 16 and 17) and with an in vitro proliferation assay. Epidermal differentiation was evaluated using immunohistochemistry (keratin 10, involucrin, loricrin, filaggrin, SPRR2, SKALP), reverse-transcriptase polymerase chain reaction (involucrin) and transmission electron microscopy (stratum corneum). Results All scars showed flattening of the epidermis. A trend of increasing epidermal thickness correlating to increasing scar abnormality was observed when comparing normal skin, normotrophic scars, hypertrophic scars and keloids. No difference in epidermal proliferation was observed. Only the early differentiation marker involucrin showed abnormal expression in scars. Involucrin was restricted to the granular layer in healthy skin, but showed panepidermal expression in keloids. Normotrophic scars expressed involucrin in the granular and upper spinous layers, while hypertrophic scars resembled normotrophic scars or keloids. Abnormal differentiation was associated with ultrastructural disorganization of the stratum corneum in keloids compared with normal skin. Conclusions Keloids showed increased epidermal thickness compared with normal skin and normotrophic and hypertrophic scars. This was not due to hyperproliferation, but possibly caused by abnormal early terminal differentiation, which affects stratum corneum formation. Our findings indicate that the epidermis is associated with keloid pathogenesis and identify involucrin as a potential diagnostic marker for abnormal scarring.

show abstract

“…Injury to skin 21 , intestine 22 , cartilage 23 , and other tissues is accompanied by inflammation and changes in HA accumulation, resulting from concurrent increased synthesis of HA itself and HA-associated proteins, such as TSG6 (encoded by Tnfaip6 ), the heavy chains of inter-alpha-trypsin inhibitor (encoded by Itih1–5 genes), and pentraxin.…”

Section: Resultsmentioning

confidence: 99%

Deficiency of hyaluronan synthase 1 (Has1) results in chronic joint inflammation and widespread intra-articular fibrosis in a murine model of knee joint cartilage damage

Chan

Xiao

et al. 2015

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

Objective Articular cartilage defects commonly result from traumatic injury and predispose to degenerative joint diseases. To test the hypothesis that aberrant healing responses and chronic inflammation lead to osteoarthritis, we examined spatiotemporal changes in joint tissues after cartilage injury in murine knees. Since intra-articular injection of hyaluronan (HA) can attenuate injury-induced osteoarthritis in wild-type (WT) mice, we investigated a role for HA in the response to cartilage injury in mice lacking HA synthase 1 (Has1−/−). Design Femoral groove cartilage of WT and Has1−/− mice was debrided to generate a non-bleeding wound. Macroscopic imaging, histology, and gene expression were used to evaluate naïve, sham-operated, and injured joints. Results Acute responses (1–2 weeks) in injured joints from WT mice included synovial hyperplasia with HA deposition and joint-wide increases in expression of genes associated with inflammation, fibrosis, and extracellular matrix (ECM) production. By 4 weeks, some resurfacing of damaged cartilage occurred, and early cell responses were normalized. Cartilage damage in Has1−/− mice also induced early responses; however, at 4 weeks, inflammation and fibrosis genes remained elevated with widespread cartilage degeneration and fibrotic scarring in the synovium and joint capsule. Conclusions We conclude that the ineffective repair of injured cartilage in Has1−/− joints can be at least partly explained by the markedly enhanced expression of particular genes in pathways linked to ECM turnover, IL-17/IL-6 cytokine signaling, and apoptosis. Notably, Has1 ablation does not alter gross HA content in the ECM, suggesting that HAS1 has a unique function in the metabolism of inflammatory HA matrices.

show abstract

Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin

Cited by 24 publications

References 22 publications

Hyaluronan in wound healing: Rediscovering a major player

Hyaluronan in wound healing: Rediscovering a major player

Increased epidermal thickness and abnormal epidermal differentiation in keloid scars

Deficiency of hyaluronan synthase 1 (Has1) results in chronic joint inflammation and widespread intra-articular fibrosis in a murine model of knee joint cartilage damage

Contact Info

Product

Resources

About