Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin

Radiation-induced fibrosis is a common side-effect of cancer treatment. The pathophysiological events leading to fibrosis are not known in detail. We analysed the effect of therapeutic irradiation on human skin collagen synthesis, skin thickness, gelatinases and their inhibitors. Twenty randomly chosen women who had been treated for breast cancer with surgery and radiation therapy participated in the study. In each patient, the irradiated skin area was compared with a corresponding non-treated skin area. Suction blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP), tissue inhibitors of matrix metalloproteinases (MMPs) 1 and 2 (TIMP-1 and TIMP-2) and MMP-9 and MMP-2/TIMP-2 complex. Skin biopsies were analysed for PINP and immunohistochemical staining was used for PIIINP. In irradiated skin, PINP, PIIINP, TIMP-1 and MMP-2/TIMP-2 complex levels in SBF and the number of PINP-positive fibroblasts in tissue sections were significantly higher in comparison with non-treated skin. The levels of TIMP-2 in irradiated and non-irradiated skin were similar. MMP-9 could not be detected in SBF with the assay used. The serum levels of MMP-9 were higher in the treated subjects than the reference values. The serum values of PINP, PIIINP, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were not significantly affected. These results indicate increased local collagen synthesis and accumulation of connective tissue in irradiated skin. The marked upregulation of collagen synthesis as a result of irradiation offers a possibility to treat this complication with compounds such as topical steroids which downregulate collagen synthesis.     

IL-4 expression by neutrophils in psoriasis lesional skin upon high-dose UVB exposure

BACKGROUND: Upon a single high dose of UVB irradiation of psoriatic lesional skin, IFN-gamma expression is decreased, whereas IL-4 expression is enhanced. A similar type 1 to type 2 shift was found in dermal T cells derived from irradiated lesional skin as compared to unexposed lesional psoriatic skin. We have found recently that the IL-4 protein detected in situ upon UVB exposure of normal skin was not associated with T cells but with infiltrating neutrophils. OBJECTIVE: To determine which cell types express IL-4 in psoriatic skin after UVB irradiation. METHODS: Skin biopsies were obtained from healthy controls and psoriasis patients before and after local UVB exposure. Double immunohistochemical stainings were performed to determine the identity of IL-4-expressing cells. RESULTS: In the irradiated skin of both healthy controls and patients, IL-4-positive cells coexpressed elastase and CD15, but not CD3. CONCLUSION: IL-4-expressing cells found in psoriatic skin after a single high-dose UVB exposure appeared to be neutrophils.     

Smoking and skin: a study of the physical qualities and histology of skin in smokers and non-smokers

Tobacco smoke is toxic to cells and could be a factor contributing to accelerated skin ageing. The aim of this study was to provide new information on the possible effects of smoking on the physical qualities of skin and the morphology of elastic fibres. The study population consisted of 98 men, including 47 current smokers and 51 never-smokers. Skin thickness and elasticity were measured from cheek, temple, abdomen, dorsal forearm and non-sun-exposed upper inner arm. Verhoeff-stained punch biopsies from the non-sun-exposed upper inner arm were assessed with a computerized image analyser in a blinded fashion to assess the amount and width of elastic fibres. The thickness of cheek skin was increased in the smokers, but skin thickness in other measured sites did not differ between the groups. The amount and width of elastic fibres in the sun-protected skin of the smokers and non-smokers did not differ significantly, nor did skin elasticity in this or any other region under evaluation, suggesting that smoking alone affects neither the amount and width of dermal elastic fibres nor the elasticity of skin in male smokers.     

强脉冲光照射对小鼠皮肤胶原纤维、弹性纤维及透明质酸含量的影响

目的 探讨强脉冲光照射对昆明小鼠皮肤胶原纤维、弹性纤维、透明质酸含量的意义。方法用强脉冲光照射小鼠右侧背部皮肤,左侧为对照,取各时间点照射组和对照组皮肤进行组织学观察,包括HE染色、Ⅰ型和Ⅲ型胶原纤维饱和苦味酸-天狼猩红染色、弹性纤维Gomori醛品红法染色,同时提取皮肤组织,碱水解-分光光度法测定羟脯氨酸含量,放射免疫法测定透明质酸含量。结果 照射后2周,真皮厚度较对照组增加（t = 4.623,P < 0.05）,4周时达最大值,较对照组增加18.71%,8周时仍大于对照组,差异有统计学意义（t = 3.904,P < 0.05）。照射后1周,Ⅲ型胶原纤维较对照组增加40.54%（t = 5.129,P < 0.05）,照射后2周和4周,Ⅰ型和Ⅲ型胶原纤维均较对照组增多明显,至8周时,均大于对照组（P < 0.05）。照射后2 ~ 8周,弹性纤维均较对照组增多（P < 0.05）;照射后1 ~ 8周,羟脯氨酸含量均较对照组增多（P < 0.05）。照射后1 d和3 d,透明质酸含量显著增加,1 ~ 8周,渐进性降低,但均高于对照组（P < 0.05）。结论 强脉冲光照射小鼠皮肤可刺激真皮胶原纤维、弹性纤维、透明质酸含量增加。     

Coordinate upregulation of tenascin C expression with degree of photodamage in human skin

Tenascin C is a large extracellular matrix glycoprotein involved in morphogenesis and wound healing. The distribution and expression levels of tenascin were examined in photodamaged skin to investigate the hypothesis that photoaged skin displays characteristics of wound repair. In situ hybridization and semiquantitative immunohistochemistry were performed on paired skin biopsies from patients with varying levels of photodamage, using monoclonal antibodies and cRNA probes for tenascin and its large isoform. In sun-protected skin, tenascin protein was distributed adjacent to the dermoepidermal junction, usually sparsely and discontinuously; tenascin mRNA was detected in dermal fibroblasts and some keratinocytes. In photodamaged skin, tenascin protein was increased in proportion to the clinical level of photodamage (analysis of variance: P < 0.0001, n = 29). With increased photodamage, tenascin protein expression became continuous along the dermoepidermal junction, extending deeper into and sometimes throughout the papillary dermis; tenascin mRNA was detected throughout the epidermis. Large tenascin isoform protein and mRNA distribution mirrored that of pantenascin, suggesting that it may be the predominant species in photodamaged skin. There was no correlation between tenascin expression levels and age or sex, and no seasonal variation was noted. The results indicate that photodamaged skin demonstrates tenascin increases consistent with an early wound healing response. However, tenascin increases in photodamage appear to be permanent and may therefore interfere with effective repair of ultraviolet-induced damage. In conclusion, this study has shown that dermal tenascin expression increases in proportion to the degree of photodamage. In normal skin, the temporal and spatial patterns of tenascin expression during morphogenesis and tissue remodelling are crucial to their correct progression. In photoageing, the 'normal' control of tenascin expression seems to be abrogated.     

Immunohistochemical studies on vitronectin in elastic tissue disorders, cutaneous amyloidosis, lichen ruber planus and porphyria

Vitronectin, identical with serum-spreading factor and S-protein of complement, is a glycoprotein present in both plasma and tissue. It stimulates cell adhesion and spreading and affects the complement and coagulation pathways. Vitronectin immunoreactivity was recently found in conjunction with dermal and renal elastic fibres, in renal amyloid deposits in cases of AL- and AA-amyloidosis, and in sclerotic glomerular lesions. Skin specimens from lesions of patients with selected skin diseases were investigated with an avidin-biotin peroxidase technique using both monoclonal and polyclonal anti-vitronectin antibodies and an alkaline phosphatase anti-alkaline phosphatase technique using monoclonal anti-vitronectin antibodies. Vitronectin immunoreactivity was found in association with the abnormal elastic tissue in solar elastosis and pseudoxanthoma elasticum. It was also found in conjunction with dermal amyloid deposits in primary localized cutaneous amyloidosis and in Civatte bodies in cases of lichen ruber planus. In cases of erythropoietic protoporphyria and porphyria cutanea tarda, hyaline perivascular deposits also demonstrated positive vitronectin immunoreactivity. The presence of vitronectin immunoreactivity not only in normal and degenerated elastic fibres but also in various pathological tissue deposits suggests that vitronectin occurs both in elastic fibres and in different types of abnormal protein deposits.     

Clinical and histopathological results following TriPollar™ radiofrequency skin treatments

Introduction: Skin laxity, wrinkles and cellulite are common aesthetic problems associated with the aging process. These symptoms are due to the weakening and thinning of dermal connective tissue and the enlargement of hypodermal fat cells. The aim of this study was to evaluate the safety and efficacy of the TriPollar RF technology in reducing fat and collagen regeneration. Methods: Twelve healthy patients underwent weekly treatments on different body sites using the TriPollar technology. Treatment areas were photographed and measured and patient satisfaction was monitored. One abdominal patient consented to a series of TriPollar treatments prior to her scheduled abdominoplasty. A controlled histopathology analysis was performed on skin samples taken during the abdominoplasty procedure. Results: Histopatho-logical examination revealed marked differences between treated and non-treated abdominal skin areas. An increase of 49% in dermal thickness, focal thickening of collagen fibers and focal shrinkage of fat cells was shown following TriPollar treatments. Average patient satisfaction indicated clear satisfaction with the clinical results achieved. Conclusion: The TriPollar is a safe and effective non-invasive technology leading to skin tightening and body shaping. Histology results indicate changes at the dermal and fat layers following TriPollar treatments resulting in increased collagen regeneration and stimulated fat metabolism.     

Effect of dermal thickness, tissue composition, and body site on skin biomechanical properties

BACKGROUND/PURPOSE: Quantitative measurement of skin biomechanical properties has been used effectively in the investigation of physiological changes in tissue structure and function and to determine treatment efficacy. As the methods are applied to new questions, tissue characteristics that may influence the resultant biomechanical properties are important considerations in the research design. For certain applications, variables such as dermal thickness and subdermal tissue composition, as well as age and/or solar exposure, may influence the skin biomechanics. METHODS: We determined the influence of dermal thickness, tissue composition, and age on the skin biomechanical properties at the shoulder, thigh, and calf among 30 healthy females. We compared two devices, the Biomechanical Tissue Characterization System and the Cutometer SEM 575 Skin Elasticity Meter , to determine the effect of tissue sampling size. Dermal thickness was measured with 20 MHz ultrasound (Dermascan C) and tissue composition was inferred from anthropomorphic data. RESULTS: Skin thickness was significantly correlated with stiffness, energy absorption, and U(r)/U(f) for the shoulder. Body mass index (BMI) was significantly correlated with stiffness (negative correlation), energy absorption (positive), and skin thickness (negative) for the shoulder. Significant differences across body sites were observed. The calf was significantly different from the thigh and shoulders for all parameters (P<0.05, one-way anova). The calf had significantly lower laxity, laxity%, elastic deformation, energy absorption, elasticity, elasticity %, U(r), U(f), and U(r)/U(f) and significantly higher stiffness compared with the thighs and shoulders. sites. The thigh and shoulder sites were significantly different for all parameters except U(r)/U(f), elasticity %, laxity%, and stiffness. The dominant and non-dominant sides were significantly different. The dominant side (right for 90% of the subjects) had increased stiffness and decreased energy absorption (tissue softness, compliance) compared with the left side. A significant (P< or =0.02) negative relationship with age was seen for all biomechanical measures except stiffness at the shoulder. For the thigh and calf sites, significant negative correlations with age were found for elasticity %, U(r), and U(r)/U(f). Age and skin thickness were not correlated in this population. Skin thickness and age influenced the energy absorption at the shoulder site. The biological elasticity at the calf site could be predicted by age and BMI. The biological activity at the thigh site could be predicted by skin thickness and BMI. CONCLUSIONS: Significant regional variations in biomechanical properties and dominant side effects were observed. The biomechanical properties were significantly influenced by age. Certain properties varied with dermal thickness and tissue composition. The parameters were well correlated between the two instruments. The Cutometer, with its smaller aperture, was found to be more sensitive to age relationships.     

Targeted overexpression of the angiogenesis inhibitor thrombospondin-1 in the epidermis of transgenic mice prevents ultraviolet-B-induced angiogenesis and cutaneous photo-damage

Chronic ultraviolet-B irradiation of the skin results in epidermal hyperplasia, degradation of extracellular matrix molecules, and formation of wrinkles. To characterize the biologic role of the vascular system in the mediation of ultraviolet-B-induced skin damage, we performed quantitative analyses of cutaneous blood vessels of mice after 10 wk of ultraviolet-B irradiation. Skin vascularization was greatly increased after chronic ultraviolet-B exposure with a significant increase of both the number and the size of dermal blood vessels, associated with upregulation of vascular endothelial growth factor expression in the hyperplastic epidermis. To directly study whether inhibition of angiogenesis may diminish ultraviolet-B-induced cutaneous damage, wild-type and transgenic mice with skin-specific overexpression of the endogenous angiogenesis inhibitor thrombospondin-1 were subjected to the same ultraviolet-B irradiation regimen. Ultraviolet-B-irradiated thrombospondin-1 transgenic mice showed a significantly reduced skin vascularization, decreased endothelial cell proliferation, and increased endothelial cell apoptosis rates, compared with wild-type mice. Moreover, dermal photo-damage and wrinkle formation were greatly reduced in thrombospondin-1 transgenic mice. These results reveal an important role of the cutaneous vascular system in mediating ultraviolet-B-induced skin damage and suggest inhibition of angiogenesis as a potential new approach for the prevention of chronic cutaneous photo-damage.     

Adult human skin maintained in organ culture: I. The ultrastructure of the acellular compartment of connective tissue.

Collagenolytic enzymes are produced by cultured skin explants. During cultivation the acellular compartment of the dermal connective tissues is digested away. The ultrastructure of the connective tissue resorption has been studied in human skin maintained in organ culture for 2--10 weeks. The connective tissue changes are: (1) Collagen fibrils with normal axial periodicity but decreasing diameters. On cross sections these fibrils have irregular outlines, while the longitudinal sections show fibrils separated into thin bundles of filaments 40--80 A thick with preserved normal axial periodicity. (2) Cross-banded filamentous aggregations (CBFA) consisting of fine parallel filaments 25 A thick and without axial periodicity. The CBFA has 350 A thick bands at 525 A intervals. At the end of the cultivation, the CBFA are replaced by solitary filaments 25 A thick. (3) The elastic fibres show no marked changes of the amorphous matrix, while the fibrils disappear. The loss of collagen and elastic fibrils during cultivation of the skin gives direct evidence of connective tissue degradation. The described changes are discussed in relation to previous ultrastructural studies on connective tissue resorption of various tissues.     

Carbon dioxide laser treatment promotes repair of the three-dimensional network of elastic fibres in rat skin

BACKGROUND: We have previously reported that ultraviolet (UV) B irradiation induces a loss of linearity in the three-dimensional structure of dermal elastic fibres, which results in the reduction of elastic properties of the skin and leads to wrinkle formation. We further reported that repair of wrinkles by all-trans retinoic acid is accompanied by recovery of the linearity of elastic fibres. Carbon dioxide (CO2) lasers are widely used for treating wrinkles in cosmetic surgery. OBJECTIVES: To perform CO2 laser treatment of wrinkles induced in rat skin by UVB irradiation and to evaluate changes in the three-dimensional structure of dermal elastic fibres during wrinkle repair. METHODS: Wrinkles were induced in the hind limb skin of Sprague-Dawley rats by UVB irradiation (130 mJ cm-2 three times weekly for 6 weeks), followed by CO2 laser treatment (11.3 J cm-2). The surface appearance of the skin was evaluated by replica observation 6 and 10 weeks after CO2 laser treatment followed by measurement of mechanical properties using a Cutometer. Subsequently, perfusion fixation and digestion with formic acid were performed and elastic fibres were observed by scanning electron microscopy (SEM). Image analysis of SEM micrographs was carried out to evaluate the linearity in the three-dimensional structure of elastic fibres. RESULTS: Six weeks after CO2 laser treatment, all parameters of skin mechanical properties in the UVB-irradiated group recovered to levels of the control non-irradiated group, accompanied by repair of wrinkles and a significant increase in linearity of the three-dimensional structure of elastic fibres. CONCLUSIONS: These findings indicate that CO2 laser treatment has a therapeutic potential to repair wrinkles to non-irradiated levels through recovery of the three-dimensional structure of elastic fibres.     

Morphometric analysis of elastic skin fibres from patients with: cutis laxa, anetoderma, pseudoxanthoma elasticum, and Buschke–Ollendorff and Williams–Beuren syndromes

Computed morphometric analysis of elastic skin fibres in patients with cutis laxa, anetoderma, Williams-Beuren syndrome, pseudoxanthoma elasticum (PXE), and Buschke-Ollendorff syndrome, all clinically ascertained, was performed and compared with data obtained from healthy individuals of the same age. The diameters, area fractions (AA%) and volume fractions (VV%) occupied by pre-elastic fibres and dermal elastic fibres were determined. Irrespective of age the diameter of dermal elastic fibres followed a Gaussian distribution for all groups studied. These diameters were taken into consideration for VV% determinations. Compared with data from skin of healthy subjects of similar age range, VV% of pre-elastic fibres was significantly decreased in patients with cutis laxa, anetoderma, Williams-Beuren syndrome, and PXE and undetectable in Buschke-Ollendorff patients. VV% of dermal elastic fibres was four- to fivefold increased in Buschke-Ollendorff syndrome, two- to threefold increased in PXE skin, four- to fivefold decreased in cutis laxa and anetoderma skin and about twofold decreased in Williams-Beuren skin. The diameter of oxytalan fibres was decreased in anetoderma and Williams-Beuren syndrome while oxytalan fibre diameter was unchanged in PXE and cutis laxa. The diameter of dermal elastic fibres was increased in PXE and Buschke-Ollendorff syndrome, but was decreased in anetoderma and Williams-Beuren syndrome and unchanged in cutis laxa. We demonstrated that cutis laxa, anetoderma, Williams-Beuren syndrome, PXE, and Buschke-Ollendorff syndrome could be easily differentiated by morphometric analysis of elastic skin fibres. Thus we propose that morphometric analyses together with skin biopsies are a valuable tool for distinguishing between inherited and/or acquired skin diseases known to display alterations of elastic fibres.     

Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes

Elastic fibers in the extracellular matrix are an integral component of dermal connective tissue. The resilience and elasticity required for normal structure and function of the skin may be attributed to the network of elastic tissue. Advances in our understanding of elastic tissue physiology provide a foundation for studying the pathogenesis of elastic tissue disorders. Many acquired disorders are nevertheless poorly understood due to the paucity of reported cases. Several acquired disorders in which accumulation or elastotic degeneration of dermal elastic fibers produces prominent clinical and histopathologic features have recently been described. They include elastoderma, linear focal elastosis, and late-onset focal dermal elastosis and must be differentiated from better-known disorders, among them acquired pseudoxanthoma elasticum, elastosis perforans serpiginosa, and Favré-Racouchot syndrome. Learning objective At the conclusion of this learning activity, participants should understand the similarities and differences between acquired disorders of elastic tissue that are characterized by an increase in elastic tissue, as well as the spectrum of solar elastotic dermatoses.     

Generalized acquired cutis laxa associated with coeliac disease: evidence of immunoglobulin A deposits on the dermal elastic fibres

Summary Acquired cutis laxa (ACL) is an uncommon elastolytic disorder of unknown aetiology. In rare instances. ACL has been reported in association with autoimmune diseases and dermal deposit of immunoglobulins, suggesting that destruction of elastic tissue may be immunologically mediated. We report a 35-year-old man with generalized acquired cutis laxa (GACL) associated with a persistent papular erythematous eruption that histopathologically showed some resemblance to dermatitis herpetiformis. A marked reduction and degeneration of dermal elastic fibres was noted in biopsies from loose-hanging skin. Direct immunofluorescence from non-inflammatory loose skin revealed granular immunoglobulin A (IgA) deposits at the basement membrane zone and fibrillar IgA deposits in the dermal papillae. IgA deposits were also observed on the elastic fibres of the reticular dermis. Electron microscopy of skin from the submammary fold revealed fragmented elastic fibres, partial absence of peripheral microfibrils and abundant neutrophils, some of which were degranulated and adjacent to elastic fibres. Immunoelectron microscopy of an erythematous papule revealed IgA deposits around dermal elastic fibres. Antigliadin, antireticulin and antiendomysium antibodies were present. Jejunal biopsies showed a gluten-sensitive enteropathy. A possible IgA-mediated immune mechanism for the development of GACL in our patient is suggested.     

Increment of subcutaneous adipose tissue is associated with decrease of elastic fibres in the dermal layer

Obesity is a significant risk factor for various skin disorders, including pressure ulcer and delayed wound healing. We previously showed that increment of subcutaneous adipose tissue contributes to poor skin condition by decreasing dermal elasticity. Here, we examined the mechanism involved. Histologic observation of abdominal skin from middle‐aged females with a wide range of body mass index (BMI), an indicator of subcutaneous fat mass, showed that dermal elastic fibre abundance was significantly decreased with increment of BMI. Concomitantly, adipocytes were significantly enlarged. Adipocyte enlargement was significantly negatively correlated with dermal elastic fibre abundance. We hypothesized that enlarged adipocytes negatively influence dermal elastic fibres, so we investigated elastic fibre‐degrading factors in in vitro‐cultured enlarged adipocytes. MMP9 gene expression and secretion were significantly increased; further, these changes were blocked by extracellular signal‐regulated kinase (ERK) inhibitor. Nuclear translocation (activation) of AP‐1, a downstream ERK signalling molecule, was also observed in enlarged adipocytes. MMP9 abundance was significantly increased in skin of subjects with high BMI and enlarged adipocytes. These results suggest that increment of subcutaneous adipose tissue leads to adipocyte enlargement together with increased degradation of dermal elastic fibres, mediated at least in part by an ERK signalling‐mediated increase of MMP9 in enlarged adipocytes.     

Connective tissue alterations in the skin of ultraviolet irradiated hairless mice

Connective tissue alterations were induced in hairless mouse skin by ultraviolet (UV) irradiation. Hairless mice were irradiated three times a week for 10 weeks with sunlamps (UVA and UVB) and the skin was examined using immunochemical and biochemical techniques. Indirect immunofluorescence was performed with antibodies directed against elastin, microfibrillar proteins, and fibronectin. Increased fluorescence was observed in the actinically damaged skin for elastin, microfibrillar proteins, and fibronectin. The elastic fiber components, elastin and microfibrillar proteins, were then isolated and quantified. Control skin contained approximately 0.1% by dry weight of elastic fiber components, whereas actinically damaged skin contained 0.2% by dry weight. These data are consistent with previous observations of elastic fiber hyperplasia in UV irradiated mice. In addition, irradiated mouse skin contained 1.12 mg of extracted fibronectin per gram wet weight as compared with 0.59 mg in control skin. Irradiated mouse skin contained increased quantities of hyaluronic acid and chondroitin sulfate (uronic acid content). These studies further support the validity of the UV irradiated hairless mouse as a model of human dermal photoaging.     

Dermatitis herpetiformis bodies. Ultrastructural study on the skin of patients using direct preembedding immunogold labeling

Skin samples from three adult patients with dermatitis herpetiformis (DH) and granular IgA deposits in the papillary tips were studied using ultrastructural immunogold technique. IgA positive, so-called DH bodies were identified as amorphous clumps--most probably immunocomplex aggregates--scattered throughout the upper papillary dermis. Dermatitis herpetiformis bodies were seen underneath the basement membrane, sometimes along microfibrillar bundles, as well as adjacent to the papillary collagen fibers and within the surface (microfibrillar) region of elastic tissue. Some DH bodies, however, were not related to any fibrillar components. The collagen and elastic fibers, microfibrillar bundles, anchoring fibrils, and elastic microfibrils themselves were unlabeled. Dermatitis herpetiformis bodies were not found in normal human skin. The results of our ultrastructural study indicate that DH bodies either are bound to a nonfibrillar component of dermal connective tissue or represent deposits of immune complexes trapped in DH skin.     

Expression of extracellular matrix proteins in reticular variant of mid‐dermal elastolysis

Background Mid‐dermal elastolysis (MDE) is a rare disorder of the elastic tissue that is characterized histopathologically by selective loss of elastic fibres in the mid dermis. Objective We aimed to investigate the protein and mRNA expression of extracellular matrix‐related proteins and growth factors in the skin (lesional and non‐lesional) of a female patient with the reticular variant of MDE. Methods Real‐time RT‐PCR and immunohistochemistry was performed for matrix metalloproteinase‐1 (MMP‐1), tissue inhibitor of metalloproteinase‐1, decorin, biglycan, versican, fibronectin, elastin, extracellular matrix protein 1, cathepsin G, transforming growth factor ß1 and connective tissue growth factor. Results Although protein expression of decorin, biglycan and versican was reduced in the mid dermis of lesional skin, mRNA expression did not differ between lesional and non‐lesional skin. As expected, elastin expression was significantly diminished in the mid dermis of lesional skin, whereas mRNA expression levels of elastin were equal to non‐lesional skin. Immunoreactivity of MMP‐1 was increased in lesional upper and mid dermis. Accordingly, MMP‐1 mRNA was also significantly higher expressed in MDE when compared with non‐lesional skin. Conclusions The results of this study confirm data of the previous investigations indicating that increased MMP‐1 activity followed by elastin degradation seems to constitute the pathogenetic background of MDE.