transforming-growth-factor-beta and Pressure-Ulcer

Skin is a key organ maintaining internal homeostasis by performing many functions such as water loss prevention, body temperature regulation and protection from noxious substance absorption, microorganism intrusion and physical trauma. Skin ageing has been well studied and it is well known that physiological changes in the elderly result in higher skin fragility favouring the onset of skin diseases. For example, prolonged and/or high-intensity pressure may suppress local blood flow more easily, disturbing cell metabolism and inducing pressure injury (PI) formation. Pressure injuries (PIs) represent a significant problem worldwide and their prevalence remains too high. A higher PI prevalence is correlated with an elderly population. Newborn skin evolution has been less studied, but some data also report a higher PI prevalence in this population compared to older children, and several authors also consider this skin as physiologically fragile. In this review, we compare the characteristics of newborn and elderly skin in order to determine common features that may explain their fragility, especially regarding PI risk. We show that, despite differences in appearance, they share many common features leading to higher fragility to shear and pressure forces, not only at the structural level but also at the cellular and molecular level and in terms of physiology. Both newborn and elderly skin have: (i) a thinner epidermis; (ii) a thinner dermis containing a less-resistant collagen network, a higher collagen III:collagen I ratio and less elastin; (iii) a flatter dermal-epidermal junction (DEJ) with lower anchoring systems; and (iv) a thinner hypodermis, resulting in lower mechanical resistance to skin damage when pressure or shear forces are applied. At the molecular level, reduced expression of transforming growth factor β (TGFβ) and its receptor TGFβ receptor II (TβRII) is involved in the decreased production and/or increased degradation of various dermal extracellular matrix (ECM) components. Epidermal fragility also involves a higher skin pH which decreases the activity of key enzymes inducing ceramide deficiency and reduced barrier protection. This seems to be correlated with higher PI prevalence in some situations. Some data also suggest that stratum corneum (SC) dryness, which may disturb cell metabolism, also increases the risk of PI formation. Besides this structural fragility, several skin functions are also less efficient. Low applied pressures induce s

Topics: Adolescent; Adult; Aged; Child; Collagen; Extracellular Matrix; Humans; Infant, Newborn; Pressure Ulcer; Skin Physiological Phenomena; Transforming Growth Factor beta; Vascular Diseases

Pressure ulcers (PU) are wounds located mainly on bone surfaces where the tissue under pressure suffers ischemia leading to cellular lesion and necrosis , its causes and the healing process depend on several factors. The aim of this study was evaluating the gene expression of inflammatory/reparative factors: IL6, TNF, VEGF, and TGF, which take part in the tissue healing process under effects of low-level laser therapy (LLLT). In order to perform lesion area analysis, PUs were photographed and computer analyzed. Biochemical analysis was performed sa.mpling ulcer border tissue obtained through biopsy before and after laser therapy and quantitative real-time PCR (qRT-PCR) analysis. The study comprised eight individuals, mean age sixty-two years old, and sacroiliac and calcaneous PU, classified as degree III and IV according to the National Pressure Ulcer Advisory Panel (NPUAP). PUs were irradiated with low-level laser (InGaAIP, 100 mW, 660 nm), energy density 2 J/cm

Topics: Biomarkers; Diabetes Mellitus; Female; Gene Expression Regulation; Granulation Tissue; Humans; Inflammation; Interleukin-6; Low-Level Light Therapy; Male; Middle Aged; Pressure Ulcer; Real-Time Polymerase Chain Reaction; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Wound Healing

The aim of the present study was to compare the therapeutic effects of activated platelet-rich plasma (PRP) prepared from elderly individuals and young adults to treat pressure ulcers (PUs), and to accumulate a theoretical basis for allogeneic PRP treatment of PUs in elderly patients.. Whole blood was extracted from elderly individuals aged >65 y and young adult volunteers for PRP preparation, and platelet concentrations in whole blood and PRP were compared. Growth factors released from activated PRP were assayed using the enzyme-linked immunosorbent assay. C57BL/6 mice were divided into three groups: the control saline, elderly-PRP (Group A), and young adult-PRP (Group B). Ischemia-reperfusion injury-induced PUs were established on the backs of mice. PUs were photographed on days 0, 5, and 10 to assess their sizes. Specimens were collected on day 10 and subjected to hematoxylin and eosin and Masson's staining. Immunohistochemical staining for CD31 was conducted to evaluate vascular formation, and cell invasion was assessed using a Transwell assay. The action of PRP on transforming growth factor-beta (TGF-β)-dependent fibroblast activity and epithelial-mesenchymal transition was analyzed using immunofluorescence and Western blotting in vitro.. The platelet concentrations in whole blood and PRP of young adults were significantly higher than that in elderly individuals. The two PRP treatment groups had similar platelet enrichment coefficients of PRP. After activation, PRP from young adults produced significantly higher levels of platelet-derived growth factor, TGF-β, and vascular endothelial growth factor than PRP from elderly individuals (P < 0.05). The concentrations of platelet-derived growth factor, TGF-β, and vascular endothelial growth factor were positively correlated with the platelet concentrations in whole blood and PRP. The effects of PRP in regulating the expressions of TGF-β, α-smooth muscle actin, vimentin, and E-cadherin were observed in vivo and in vitro. The two PRP treatment groups exhibited better wound healing than the control group, as evidenced by more re-epithelialization, higher collagen content, skin fibrosis, and more blood vessel formation over time. Group B exhibited better wound healing than Group A (P < 0.05).. PRP exhibits potent wound healing ability in PU therapy, and PRP from young adults is seemingly superior to that from elderly individuals because of a higher concentration of platelets and increased production of growth factors.

Topics: Aged; Animals; Humans; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred C57BL; Platelet-Derived Growth Factor; Platelet-Rich Plasma; Pressure Ulcer; Suppuration; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Young Adult

Patients with spinal cord injury have a predisposition to develop pressure ulcers. Specific characteristics of the patients' skin potentially involved have not yet been identified. The purpose of this investigation was to determine whether loss of neuronal control affects cellular and molecular homeostasis in the skin. Intact afflicted skin, wound edge of pressure ulcers, and control skin were analysed. Platelets, transforming growth factor-β1, and activin A were identified by immunohistochemistry. Transforming growth factor-β-like activity was determined by bioassay, and gene expression by DNA microarray analysis or RT-PCR. In afflicted skin, enhanced platelet extravasation was detected. Transforming growth factor-β1 and activin A accumulated in the dermal-epidermal junction zone. Transforming growth factor-β-like activity and activin A expression were increased in intact afflicted skin (compared to control skin) and were further enhanced in pressure ulcers. In vitro, activity was generated by fibroblast-epithelial cell interactions, which also induced activin A. Thus, loss of neuronal control in spinal cord injury appears to trigger inappropriate wound healing processes in the patients' skin. Plasma leakage and increased transforming growth factor-β-like activity combined with shear forces potentially enhance the risk for pressure ulcer formation.

Topics: Humans; Pressure Ulcer; Skin; Spinal Cord Injuries; Transforming Growth Factor beta; Wound Healing

The Vacuum Assisted Closure device (V.A.C.) is commonly used for the treatment of problematic wounds. Furthermore, wound fluid can be easily collected with this device for research purposes. However, there is inadequate information as to whether the measurement of biomoieties of importance to wound healing is affected by the exposure of wound fluid to V.A.C. components, namely Polyurethane-foam and tubing. This study is an attempt to evaluate whether exposure of wound fluid to either V.A.C.-components affects concentrations of transforming growth factor beta 1 (TGF-b1) in wound fluid.. Wound fluid was gathered from five decubital ulcer patients using the foil-technique and was exposed to sterile pieces of the V.A.C. Polyurethane-foam, tubing material or nothing for zero, one or five hours. Saline served as control. The concentration of TGF-b1 was measured using sandwich-ELISA. The resulting data were analyzed using two-way ANOVA, Newman-Keuls and Bonferroni t-Test.. The concentration of TGF-b1 decreased significant in all three groups during the five hours of the experiment (p < 0.05). There was no significant decrease in TGF-b1 concentration at any time point in-between the groups.. From this study, we conclude that wound-fluid collected from the V.A.C.-device via the polyurethane-foam or tubing for purposes of analyzing concentrations of TGF-beta 1 should not be different from fluid collected using the foil technique.

Topics: Debridement; Enzyme-Linked Immunosorbent Assay; Equipment Design; Exudates and Transudates; Humans; Microcomputers; Occlusive Dressings; Polyurethanes; Pressure Ulcer; Surgery, Computer-Assisted; Suture Techniques; Transforming Growth Factor beta; Transforming Growth Factor beta1; Vacuum; Wound Healing

Heterotopic Ossification (HO) occurs as a consequence of several diseases and of various forms of trauma. HO is particularly frequent in paraplegic patients with spinal cord lesions. It is obvious that extraskeletal cells are able to differentiate into an osteogenic direction. However, the mechanisms of the induction process of HO and the stimulating agents are not precisely known. A novel tool for studying the ossification process at the level of transcription is the technique of non-radioactive in situ hybridisation. Using digoxigenin labeled cDNA probes we investigated the distribution patterns of types I, II and III collagen mRNAs and the mRNA of Transforming Growth Factor beta 1 (TGF-beta 1) in heterotopic ossification of pressure sores of paraplegic patients. The three collagen mRNAs as well as the TGF-beta 1 mRNA exhibited substantially divergent distribution patterns. Type I (alpha 1) collagen mRNA was predominantly detectable in preosteoblasts, chondroblasts and chondrocytes of the ossification zone. Type II (alpha 1) collagen mRNA was nearly exclusively found in cells of the chondrogenic lineage. Type III (alpha 1) collagen mRNA was detectable at low levels in soft tissue, but was strongly expressed by chondroblasts and chondrocytes of heterotopic cartilage. In contrast expression of TGF-beta 1 mRNA was found in a spatial different distribution pattern in areas of proliferation of mesenchymal tissue and in different stages of ectopic bone formation. As in the case of collagen Type I (alpha 1) and III (alpha 1) mRNAs the maximum of localization of TGF-beta 1 was detected in chondroblastic areas of heterotopic ossification. Taken together our in situ hybridization experiments provide evidence that chondrogenic cells play a central role in the process of HO with a phenotypic alteration in collagen type expression and a strong expression of TGF-beta 1 mRNA. These findings support individual in vivo function for TGF-beta 1 in local cellular regulation of ectopic bone formation.

Topics: Cartilage; Collagen; Collagen Type I, alpha 1 Chain; DNA Probes; Humans; In Situ Hybridization; Ossification, Heterotopic; Osteoblasts; Paraplegia; Phenotype; Pressure Ulcer; RNA, Messenger; Transforming Growth Factor beta

Exogenously applied transforming growth factor-beta (TGF-beta) isoforms enhance wound healing processes in animal models; however, little is known about the expression of endogenous TGF-beta s and TGF-beta receptors in intact human skin or during wound healing. The present study has revealed several unexpected findings by means of in situ hybridization and immunohistology techniques. In humans, TGF-beta 3 is constitutively expressed in the epidermis of intact skin and in that of acute and chronic wounds--a pattern of expression closely mirrored by the TGF-beta type II receptor. Although not detected in intact skin, TGF-beta 1 mRNA expression was observed in the regenerating epidermis of acute (thermal) wounds but was not found in chronic decubital (pressure) wounds. TGF-beta 2 mRNA expression was not detected in the epidermis of any human skin or wound biopsies. From these findings we suggest that constitutive expression of TGF-beta 3 is important for maintenance of epidermal differentiation and that an induction of TGF-beta 1 expression is essential for re-epithelialization of human skin wounds. Lack of TGF-beta 1 expression in chronic pressure wounds may be associated with their protracted healing tendencies.

Topics: Adult; Aged; Aged, 80 and over; Humans; Immunohistochemistry; In Situ Hybridization; Keratinocytes; Pressure Ulcer; Receptors, Transforming Growth Factor beta; Regeneration; RNA, Messenger; Skin; Transforming Growth Factor beta; Wound Healing