Cleavage of hyaluronan is impaired in aged dermal wounds

Reed, May J.; Damodarasamy, Mamatha; Chan, Christina K.; Johnson, Matthew N.; Wight, Thomas N.; Vernon, Robert B.

doi:10.1016/j.matbio.2012.09.004

Cited by 21 publications

(28 citation statements)

References 54 publications

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“…There is evidence that in normal tissues, cleavage of HA into lower MW forms is altered by aging . We have found that in mice, age‐related impairments in dermal wound repair are correlated with a deficit in the production of LMW‐HA . In the nervous system, there is evidence that the presence of LMW‐HA can block inflammatory signals that potentiate encephalitis.…”

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confidence: 84%

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Hyaluronan enhances wound repair and increases collagen III in aged dermal wounds

Damodarasamy

Johnson

Bentov

et al. 2014

Wound Repair Regeneration

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Age-related changes in the extracellular matrix contribute to delayed wound repair in aging. Hyaluronan, a linear nonsulfated glycosaminoglycan, promotes synthesis and assembly of key extracellular matrix components, such as the interstitial collagens, during wound healing. The biological effects of hyaluronan are mediated, in part, by hyaluronan size. We have previously determined that dermal wounds in aged mice, relative to young mice, have deficits in the generation of lower molecular weight hyaluronan (defined as <300 kDa). Here, we tested the effect of exogenous hyaluronan of 2, 250, or 1,000 kDa sizes on full-thickness excisional wounds in aged mice. Only wounds treated with 250 kDa hyaluronan (HA250) were significantly improved over wounds that received carrier (water) alone. Treatment with HA250 was associated with increased expression of transcripts for the hyaluronan receptors CD44 and RHAMM, as well as collagens III and I. Analyses of dermal protein content by mass spectrometry and Western blotting confirmed significantly increased expression of collagen III in wounds treated with HA250 relative to control wounds. In summary, we find that HA250 improves wound repair and increases the synthesis of collagen III in aged dermal wounds.

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confidence: 84%

“…Aged (24 months old) mice received two dorsal, 6‐mm full‐thickness dermal wounds as previously described . Wounds were covered with Tegaderm (3M, St. Paul, MN) to delay wound contraction, a prominent feature of skin wound healing in rodents.…”

Section: Methodsmentioning

confidence: 99%

Hyaluronan enhances wound repair and increases collagen III in aged dermal wounds

Damodarasamy

Johnson

Bentov

et al. 2014

Wound Repair Regeneration

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“…HA reactivity was quantitated according to a standard curve of purified HA (Underhill 1993; Wilkinson et al 2004; Jarvelainen et al 2009). The molecular weight (MW) of HA in the dialyzed, proteinase K-treated preparations was evaluated by electrophoresis through 1.2% agarose as previously described (Reed et al 2013). …”

Section: Methodsmentioning

confidence: 99%

Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation

Damodarasamy

Vernon

Chan

et al. 2014

In Vitro Cell.Dev.Biol.-Animal

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The extracellular matrix (ECM) of the prostate, which is comprised primarily of collagen, becomes increasingly disorganized with age, a property that may influence the development of hyperplasia and cancer. Collageous ECM extracted from the tails of aged mice exhibits many characteristics of collagen in aged tissues, including the prostate. When polymerized into a 3-dimensional (3D) gel, these collagen extracts can serve as models for the study of specific cell-ECM interactions. In the present study, we examined the behaviors of human prostatic epithelial cell lines representing normal prostate epithelial cells (PEC), benign prostatic hyperplasia (BPH-1), and adenocarcinoma (LNCaP) cultured in contact with 3D gels made from collagen extracts of young and aged mice. We found that proliferation of PEC, BPH-1, and LNCaP cells were all increased by culture on aged collagen gels relative to young collagen gels. In examining age-associated differences in the composition of the collagen extracts, we found that aged and young collagen had a similar amount of several collagen-associated ECM components, but aged collagen had a much greater content of the glycosaminoglycan hyaluronan (HA) than young collagen. The addition of HA (of similar size and concentration to that found in aged collagen extracts) to cells placed in young collagen elicited significantly increased proliferation in BPH-1 cells, but not in PEC or LNCaP cells, relative to controls not exposed to HA. Of note, histochemical analyses of human prostatic tissues showed significantly higher expression of HA in BPH and prostate cancer stroma relative to stroma of normal prostate. Collectively, these results suggest that changes in ECM involving increased levels of HA contribute to the growth of prostatic epithelium with aging.

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“…Hyaluronan size determines its biologic properties: high molecular weight forms can inhibit proliferation and migration of many cell types, whereas middle and lower molecular weight forms usually promote tissue formation 46 . Hyaluronan content is maintained in aged wound dermis, but its degradation is reduced 47 . Wound healing also requires matrix metalloproteinases (MMPs), which promote cell proliferation and vessel ingrowth by degrading the existing extracellular matrix.…”

Section: Iic Extracellular Matrix and Tissue Remodelingmentioning

confidence: 99%

Anesthesia, Microcirculation, and Wound Repair in Aging

Bentov¹,

Reed²

2014

Survey of Anesthesiology

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Age related changes in skin contribute to impaired wound healing after surgical procedures. Changes in skin with age include decline in thickness and composition, a decrease in the number of most cell types and diminished microcirculation. The microcirculation provides tissue perfusion, fluid homeostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause further disruption of the microvasculature of aged skin. Perioperative management can be modified to minimize insults to aged tissues. Judicious use of fluids, maintenance of normal body temperature, pain control and increased tissue oxygen tension are examples of adjustable variables that support the microcirculation. Anesthetic agents influence the microcirculation from a combination of effects on cardiac output, arterial pressure and local micro-vascular changes. We examine the role of anesthetic management in optimizing the microcirculation and potentially improving postoperative wound repair in older persons. I. BackgroundSurgical wound repair is a major problem in the older population 1 , who are at increased risk of wound dehiscence and infection 2 . As a specific example, surgical site infections (SSI) are common (about 500,000 cases annually in the United States), lead to worse patient outcome (patients who develop SSI are twice as likely to die 3 ), and are an enormous economic burden (1-10 billion dollars annually) 4 . Many factors contribute to age related changes in skin 5 and subsequent vulnerability to impaired wound healing and infection. Changes in skin with age ( Figure 1) include a decline in epidermal and dermal thickness and composition, as well as a decrease in the number of most resident cell types. The dermalepidermal junction is flattened and the microcirculation is diminished 6 . The latter is defined as blood flow through arterioles, capillaries and venules and is the key system that affects the entire skin surface. In the aging patient, the skin's microcirculation is reduced by 40% between the ages of 20 to 70 years 7 . The microcirculation provides tissue perfusion, fluid hemostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause disruption of the skin's microcirculation as manifested by local edema resulting from vasodilation and increased vascular permeability. Summary StatementAged skin is at increased risk of poor post-operative wound healing. Changes in the cutaneous microcirculation with aging contribute to this risk. This review examines the role of anesthesia management on microcirculatory function. In this review, we will use skin as a representative organ to describe age-related changes that negatively affect the microcirculation and have subsequent impacts on wound healing and the incidence of postoperative infection. We will then examine the role of anesthesia management in minimizing detrimental effects on the microcirculation. A greater understanding of...

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Cleavage of hyaluronan is impaired in aged dermal wounds

Cited by 21 publications

References 54 publications

Hyaluronan enhances wound repair and increases collagen III in aged dermal wounds

Hyaluronan enhances wound repair and increases collagen III in aged dermal wounds

Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation

Anesthesia, Microcirculation, and Wound Repair in Aging

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