Wound collagenase activity correlates directly with collagen glycosylation in diabetic rats

Hennessey, Patrick J.; Ford, Edward G.; Black, Charles T.; Andrassy, Richard J.

doi:10.1016/s0022-3468(05)80167-8

Cited by 59 publications

(32 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Multiple factors exist that relate to impaired wound healing, including abnormal glucose metabolism and vascular complications. For example, hyperglycemia initiates events that result in impaired collagen synthesis (15); and impaired vascular function in diabetics is associated with thickening of the basement membrane of the capillaries and arterioles (16).…”

Section: Discussionmentioning

confidence: 99%

Wound Healing Delay in the ZDSD Rat

Suckow

Gobbett

Peterson

2017

View full text Add to dashboard Cite

Abstract. Animal It is estimated that there are more than 400 million or more people in the world suffering from diabetes mellitus (1). Many diabetic patients have difficulty in healing wounds and the annual cost to manage these wounds exceeds 20 billion dollars (2). In particular, wounds affecting the feet are common, with amputation being a frequent outcome (3). Because of the importance of impaired wound healing in diabetics, animal models of diabetic wound healing are of great interest.Rodent models of diabetic wound healing have received a great deal of focus due to ease of maintenance, cost and availability of genetically modified lines. The full-thickness excisional wound model is a standard approach in which a punch biopsy is used to remove both epidermal and dermal tissues, allowing evaluation of epithelialization, granulation, and angiogenesis, all key processes during physiological wound healing (4). Although wound healing in rodents occurs mainly by contraction, several diabetic rodent models have been used to characterize wound healing in type 2 diabetes, including the db/db mouse, the JCR:LA-cp rat and the Zucker diabetic fatty (ZDF) rat (5-8).The Zucker diabetic Sprague dawley (ZDSD) rat is an animal model of type 2 diabetes and dietary obesity which develop subsequently to chronic dietary manipulation (9, 10). ZDSD rats were developed by cross-breeding diet-induced obesity (DIO) rats derived from Sprague Dawley rats Crl:CD(SD) with ZDF +/+ lean rats. Lacking leptin receptor defects, the ZDSD rat possesses an obese phenotype and the potential to develop overt hyperglycemia between 15 and 21 weeks of age. These characteristics make the ZDSD rat an excellent model of human adult-onset diabetes which develops over time in response to chronic overeating and lack of physical activity. The studies described here were undertaken to determine if the ZDSD rat demonstrates impaired wound healing and might, therefore, be useful as an animal model of delayed healing in type-2 diabetic patients. Materials and MethodsAnimals. Four month old male rats documented to be free of common infectious pathogens were used. All studies were approved by the Institutional Animal Care and Use Committee. Rats were maintained in solid-bottom polycarbonate cages containing abundant hardwood chip bedding. ZDSD rats were obtained from PreClinOmics, Inc., (now a Crown Bioscience company; Indianapolis, IN, USA) and Hsd:Sprague Dawley ® SD ® rats were 55

show abstract

Section: Discussionmentioning

confidence: 99%

Wound Healing Delay in the ZDSD Rat

Suckow

Gobbett

Peterson

2017

View full text Add to dashboard Cite

show abstract

“…9,27,28 In vitro collagen matrices that were artificially glycated displayed a decrease in biomechanical properties when compared to nonglycated matrices both in vitro and when implanted in vivo. 29 There has also been a suggestion that collagen breakdown may be altered in the setting of diabetes due to glycation and cross linkage.…”

Section: Figure 8 Amentioning

confidence: 99%

“…MMP-2 and MMP-9 have been shown to be present in greater concentration in wounded diabetic animals than their nondiabetic littermates, which is similar to findings from patients with nonhealing ulcers. 9 Diabetes is characterized by significantly increased cross linking and nonenzymatic glycation of collagen, as well as elevated levels of advanced glycation end products (AGEs). 10,11 Blockade of the receptor for advanced glycation end products (RAGEs) can restore the wound healing properties of diabetic (Db/Db) mice.…”

mentioning

confidence: 99%

“…12 Hyperglycemic animals have been shown to have significantly higher concentrations of glycated collagen and higher levels of collagenase activity. 9,13 Furthermore, diabetic (Db/Db) mice have also been shown to have a prolonged inflammatory phase with sustained expression of the inflammatory cytokines macrophage chemoattractant protein 1 (MPC-1) and macrophage inflammatory protein 2 (MIC-2). 14 The biomechanical properties of diabetic skin are another critical aspect of wound-healing physiology.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Impaired Biomechanical Properties of Diabetic Skin

Bermudez

Herdrich

et al. 2011

The American Journal of Pathology

106

View full text Add to dashboard Cite

Diabetic skin is known to have deficient wound healing properties, but little is known of its intrinsic biomechanical properties. We hypothesize that diabetic skin possesses inferior biomechanical properties at baseline, rendering it more prone to injury. Skin from diabetic and nondiabetic mice and humans underwent biomechanical testing. Real-time PCR was performed for genes integral to collagen synthesis and degradation. MMP-2 and MMP-9, and TIMP-1 protein levels were assessed by ELISA and zymography. Collagen I and III content was assessed using Western blot analysis. At baseline, both murine and human diabetic skin was biomechanically inferior compared to nondiabetic skin, with decreased maximum stress and decreased modulus (P < 0.001 and < 0.05, respectively). Surprisingly, the expression of genes involved in collagen synthesis were significantly up-regulated, and genes involved in collagen degradation were significantly down-regulated in murine diabetic skin (P < 0.01). In addition, MMP-2 and MMP-9/TIMP-1 protein ratios were significantly lower in murine diabetic skin (P < 0.05). Collagen I levels and I:III ratios were lower in diabetic skin (P < 0.05). These findings suggest that the predisposition of diabetics to wounds may be the result of impaired tissue integrity at baseline, and are due, in part, to a defect in the regulation of collagen protein synthesis at the post-transcriptional level. Diabetes is associated with increased morbidity and mortality, 1 as well as impaired wound healing. 2 Diabetesrelated admissions accounted for 22% of all hospital inpatient days in 2007, and diabetic foot ulcers account for 20% of all hospital admissions in diabetic patients, which are the leading cause of lower extremity amputations. 2 Improvements made in diabetic wound management and prevention clearly have the potential to affect a large number of patients and decrease diabetic-related health care expenditures.More than 100 factors have been identified that contribute to the impairment in diabetic wound healing. 3 Decreased angiogenesis, 4 impaired growth factor production, 5 an altered inflammatory and immune response, 5 a decreased rate of wound contraction, 6 and an imbalance between the accumulation of extracellular components and their remodeling by matrix metalloproteinases (MMPs) 7,8 have all been demonstrated in diabetic wounds. MMP-2 and MMP-9 have been shown to be present in greater concentration in wounded diabetic animals than their nondiabetic littermates, which is similar to findings from patients with nonhealing ulcers. 9 Diabetes is characterized by significantly increased cross linking and nonenzymatic glycation of collagen, as well as elevated levels of advanced glycation end products (AGEs). 10,11 Blockade of the receptor for advanced glycation end products (RAGEs) can restore the wound healing properties of diabetic (Db/Db) mice. 12 Hyperglycemic animals have been shown to have significantly higher concentrations of glycated collagen and higher levels of collagenase activity. 9,13 Furthermore...

show abstract

“…A avaliação das MMPs -2 e -9 por zimografia nos mostrou um aumento dessas proteases na ferida diabética, corroborando estudos anteriores realizados em animais e em biópsias de úlceras crônicas humanas (BERMUDEZ et al, 2011;HENNESSEY, 1990).…”

Section: Discussionunclassified

Emprego de nanopartículas lipídicas sólidas contendo extrato de semente de uvas para aceleração da cicatrização de feridas cutâneas em camundongos diabéticos.

Florim¹

View full text Add to dashboard Cite

O estresse oxidativo causado pela hiperglicemia desempenha um importante papel no desenvolvimento e progressão do diabetes mellitus (DM) e suas complicações, como a cicatrização deficiente de feridas. O objetivo deste estudo foi avaliar os efeitos da administração tópica de nanopartículas lipídicas sólidas (NLS) contendo extrato de semente de uva sobre a cicatrização cutânea de camundongos controles e diabéticos, observando a cinética de cicatrização, alterações da matriz de colágeno e grau de estresse oxidativo. As análises morfométricas e histológicas mostraram um retardo no fechamento da ferida nos animais diabéticos ao final do 14º dia pós-lesão, acompanhado de uma resposta inflamatória inicial suprimida, mas persistente nas etapas finais do processo de reparo, bem como um atraso na deposição de colágeno fibrilar, demonstrada por coloração picrosirius. Observou-se também um aumento da atividade das metaloproteinases -2 e -9 por zimografia, um aumento de células contendo α-actina de músculo liso (análise imunohistoquímica) e um grau significativo de peroxidação lipídica na derme dos animais diabéticos, avaliada por TBARS e por imunohistoquímica para 4-hidroxi-nonenal (4-HNE). O extrato de semente de uva comercial Vitaflavan ® apresentou capacidade antioxidante e 46% de proantocianidinas totais. A NLS foi desenvolvida utilizando-se gordura de coco. A NLS branca e a NLS contendo Vitaflavan ® apresentaram características físico-químicas semelhantes e um diâmetro médio variando entre 108,8 ± 1,3 e 144 ± 13,2 nanômetros. O tratamento tópico com gel (veículo utilizado para a aplicação das NLS), com a NLS branca e com NLS associada com o extrato de semente de uva foram capazes de recuperar o atraso no fechamento da ferida observado anteriormente nos animais diabéticos, com uma melhora no recrutamento de células inflamatórias e reepitelização. Além disso, os tratamentos atenuaram a peroxidação lipídica, de forma mais acentuada com a aplicação da NLS branca e com a NLS contendo Vitaflavan ® , comprovando as suas propriedades antioxidantes. Os resultados sugerem, no entanto, que além da ação antioxidante, os efeitos positivos desta terapia estão também bastante associados à cobertura da ferida e prevenção da desidratação tecidual.Palavras-chave: Diabetes mellitus. Cicatrização. Estresse oxidativo. Antioxidantes. Proantocianidinas. Nanotecnologia. Oxidative stress caused by hyperglycemia plays an important role in the development and progression of diabetes mellitus (DM) and its complications, such as impaired wound healing. The aim of this study was to evaluate the effects of the topical administration of solid lipid nanoparticles (NLS) containing grape seed extract on cutaneous wound healing in control and diabetic mice, observing healing kinetics, changes in the collagen matrix and the degree of oxidative stress. Morphometric and histological analyzes showed a delay in wound closure in diabetic animals on the 14 th day post-injury, accompanied by an inflammatory response initially suppressed, but persistent in the la...

show abstract

Wound collagenase activity correlates directly with collagen glycosylation in diabetic rats

Cited by 59 publications

References 17 publications

Wound Healing Delay in the ZDSD Rat

Wound Healing Delay in the ZDSD Rat

Impaired Biomechanical Properties of Diabetic Skin

Emprego de nanopartículas lipídicas sólidas contendo extrato de semente de uvas para aceleração da cicatrização de feridas cutâneas em camundongos diabéticos.

Contact Info

Product

Resources

About