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1.
J Am Acad Dermatol ; 81(2): 480-488, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30954583

RESUMO

BACKGROUND: Exposure to the sun causes premature skin aging, known as photoaging. Clinical features of photoaging vary widely among individuals. In one form, skin appears thin with telangiectasia, and in another form, skin appears thickened with coarse wrinkles. Etiologic, clinical, and therapeutic distinctions among different forms of photoaging remain largely unknown. OBJECTIVE: To characterize the clinical, histologic, and molecular features of hypertrophic and atrophic photoaging. METHODS: In total, 53 individuals were clinically classified as having primarily atrophic or hypertrophic photoaging or neither (controls). Participants' demographic and sun exposure-related lifestyle data were captured by questionnaire. Fifteen clinical features of participants were qualitatively or quantitively scored. Facial biopsies were analyzed for gene expression and histologic characteristics. RESULTS: Actinic and seborrheic keratosis, telangiectasia, and prior incidence of skin cancers were statistically significantly greater and photoaging scale severity, coarse wrinkles, thickness, and sallowness were significantly reduced in atrophic versus hypertrophic groups. Histology also revealed significantly less elastotic material in atrophic photoaging. Gene expression of matrix metalloproteinases and collagens did not differ between the 2 forms of photoaging. LIMITATIONS: The study was not designed to identify other possible subtypes of photoaging. CONCLUSION: Systematic, categorical, and quantitative clinical and histologic assessments distinguish atrophic and hypertrophic photoaging.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Envelhecimento da Pele/genética , Envelhecimento da Pele/patologia , Neoplasias Cutâneas/epidemiologia , Pele/metabolismo , Pele/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia/genética , Atrofia/patologia , Biópsia , Colágeno/genética , Face , Feminino , Expressão Gênica , Humanos , Hipertrofia/genética , Hipertrofia/patologia , Incidência , Ceratose Actínica/epidemiologia , Ceratose Seborreica/epidemiologia , Estilo de Vida , Masculino , Metaloproteinases da Matriz/genética , Pessoa de Meia-Idade , Fenótipo , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação , Inquéritos e Questionários , Telangiectasia/epidemiologia , Telangiectasia/patologia , Raios Ultravioleta/efeitos adversos
2.
Invest Radiol ; 45(11): 733-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20661146

RESUMO

OBJECTIVE: Nephrogenic systemic fibrosis is a clinical syndrome occurring in a small subset of patients with end-stage renal disease (ESRD). Exposure to certain of the gadolinium-based contrast agents during magnetic resonance imaging appears to be a trigger. The pathogenesis of the disease is largely unknown. The present study addresses potential pathophysiologic mechanisms. MATERIALS AND METHODS: We have compared responses in organ-cultured skin and skin fibroblasts from individuals with ESRD to responses of healthy control subjects to Omniscan treatment. RESULTS: Treatment of skin from ESRD patients with Omniscan stimulated production of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1, but not type I procollagen. The same treatment also stimulated an increase in hyaluronan production. Similar results were seen with skin from normal controls but basal levels were higher in ESRD patients. Fibroblasts in monolayer culture gave the same responses, but there were no differences based on whether the cells were isolated from the skin of healthy subjects or those with ESRD. CONCLUSION: These data indicate that Omniscan exposure alters an enzyme/inhibitor system responsible for regulating collagen turnover in the skin and directly stimulates hyaluronan production. The higher basal levels of type I procollagen, matrix metalloproteinase-1, tissue inhibitor of metalloproteinases-1, and hyaluronan in the skin from ESRD patients could contribute to the sensitivity of this patient population to fibrotic changes, which might be induced by exposure to some of the gadolinium-based contrast agents.


Assuntos
Meios de Contraste , Fibroblastos/efeitos da radiação , Gadolínio , Falência Renal Crônica/complicações , Imageamento por Ressonância Magnética , Dermopatia Fibrosante Nefrogênica/etiologia , Pele/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Ácido Hialurônico , Falência Renal Crônica/patologia , Masculino , Metaloproteinase 1 da Matriz/efeitos da radiação , Inibidores de Metaloproteinases de Matriz , Pessoa de Meia-Idade , Dermopatia Fibrosante Nefrogênica/patologia , Técnicas de Cultura de Órgãos , Fatores de Risco
3.
Dig Dis Sci ; 53(3): 723-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17934846

RESUMO

Patients with the hamartomatous polyposis Peutz-Jeghers and familial juvenile polyposis syndromes are predisposed to colorectal cancer but lack early genetic alterations found in adenomatous premalignant lesions. We studied hamartomatous polyps for the expression of an early preneoplastic colorectal neoplasia risk marker also found in familial adenomatous polyposis patients. Retrospective, genetic, and hospital archival tissue immunohistochemistry using Adnab-9, a premalignant marker often found in Paneth-like cells (PCs), was performed on sections of polyps from eight patients with Peutz-Jeghers syndrome, eight patients with familial juvenile polyposis, and 36 hyperplastic polyp control sections. Anti-alpha-defensin 5 (AD5), a universal PC marker, was also used to label a subgroup of sections. Hamartomatous polyposis patients also underwent specific genetic analysis. Eighty-nine percent of Peutz-Jeghers syndrome polyps labeled with Adnab-9 compared with 63% for AD5; 88% of familial juvenile polyposis sections also labeled with Adnab-9. Of the 36 hyperplastic polyp sections, only four (11%) labeled with Adnab-9 and one (3%) with AD5. Adnab-9 labeling of PCs in the epithelial elements of hamartomatous colonic lesions of hereditary hamartomatous syndrome patients reflects the predisposition to colorectal cancer, further justifying early intervention strategies.


Assuntos
Polipose Adenomatosa do Colo/patologia , Anticorpos Monoclonais , Biomarcadores Tumorais , Colo/patologia , Pólipos do Colo/patologia , Síndrome de Peutz-Jeghers/patologia , Quinases Proteína-Quinases Ativadas por AMP , Polipose Adenomatosa do Colo/genética , Adolescente , Adulto , Idoso , Pré-Escolar , Pólipos do Colo/genética , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Pessoa de Meia-Idade , Processos Neoplásicos , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , alfa-Defensinas/metabolismo
4.
Am J Pathol ; 168(6): 1861-8, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16723701

RESUMO

Reduced synthesis of collagen types I and III is characteristic of chronologically aged skin. The present report provides evidence that both cellular fibroblast aging and defective mechanical stimulation in the aged tissue contribute to reduced collagen synthesis. The reduction in collagen synthesis due to fibroblast aging was demonstrated by a lower in vitro production of type I procollagen by dermal fibroblasts isolated from skin of young (18 to 29 years) versus old (80+ years) individuals (82 +/- 16 versus 56 +/- 8 ng/ml; P < 0.05). A reduction in mechanical stimulation in chronologically aged skin was inferred from morphological, ultrastructural, and fluorescence microscopic studies. These studies, comparing dermal sections from young and old individuals, demonstrated a greater percentage of the cell surface attached to collagen fibers (78 +/- 6 versus 58 +/- 8%; P < 0.01) and more extensive cell spreading (1.0 +/- 0.3 vs. 0.5 +/- 0.3; P < 0.05) in young skin compared with old skin. These features are consistent with a lower level of mechanical stimulation on the cells in old versus young skin. Based on the findings presented here, we conclude that reduced collagen synthesis in chronologically aged skin reflects at least two different underlying mechanisms: cellular fibroblast aging and a lower level of mechanical stimulation.


Assuntos
Envelhecimento , Colágeno/biossíntese , Fibroblastos/metabolismo , Envelhecimento da Pele , Pele/patologia , Adolescente , Adulto , Idoso de 80 Anos ou mais , Biópsia , Colágeno/metabolismo , Humanos , Pele/metabolismo , Estresse Mecânico
5.
Hum Pathol ; 37(4): 422-30, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16564916

RESUMO

The objective of this study was to assess matrix metalloproteinase (MMP) and MMP inhibitor expression in the airspace of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) and to determine the prognostic significance of MMP expression in this patient population. Twenty-eight patients with ALI or ARDS were prospectively enrolled in this study; bronchoalveolar lavage (BAL) fluid obtained from these patients was examined for expression of MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-8 (neutrophil collagenase), and MMP-9 (gelatinase B). Levels of MMP inhibitors (ie, tissue inhibitor of metalloproteinases-1 and -2 [TIMP-1 and TIMP-2]) were examined in parallel. Expression of MMPs was correlated with relevant clinical outcomes in patients with ALI/ARDS. In nearly all specimens obtained from patients with ALI/ARDS, there were high levels of MMP-2, MMP-8, MMP-9, and TIMP-1, but in only a small subset of patients (6/28) were there detectable levels of MMP-1 and/or MMP-3. In the patients with elevated MMP-1 and/or MMP-3, the mortality rate was higher (83%) than in the group without detectable levels of these enzymes (32%). Likewise, the overall severity of disease as indicated by Acute Physiology and Chronic Health Evaluation III scores was higher in this group (98 +/- 30) than in the group without detectable MMP-1 or MMP-3 (78 +/- 28). The percentage of individuals in whom lung disease was complicated by multiorgan failure was also higher in the group with detectable MMP-1 and/or MMP-3 (83%) than in the group without (64%), as was the number of organs that failed. In contrast, there was no correlation between MMP-1 and/or MMP-3 expression and impairment in gas exchange, as determined by the ratio of partial pressure of oxygen to fraction of inspired oxygen (Pao(2)/Fio(2)) on the day of BAL sample. Based on these findings, we conclude that elevated MMP-2, MMP-8, and MMP-9 in BAL fluid is a marker of acute lung injury (and, perhaps, a contributor to ALI) but is not necessarily an indicator of a poor outcome. On the other hand, the presence of detectable MMP-1 and/or MMP-3 is an indicator of more ominous disease progression.


Assuntos
Metaloproteinases da Matriz/metabolismo , Síndrome do Desconforto Respiratório/enzimologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Inibidores de Metaloproteinases de Matriz , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/patologia , Taxa de Sobrevida
6.
Exp Mol Pathol ; 79(2): 151-60, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16004981

RESUMO

Matrix metalloproteinases (MMPs) with collagenolytic and gelatinolytic activities are up-regulated in basal cell carcinoma. In the present study we demonstrate that the major collagenolytic enzyme detected is MMP-1 (interstitial collagenase) while gelatinolytic enzymes include both MMP-2 (72-kDa gelatinase A) and MMP-9 (92-kDa gelatinase B). Significant fractions of all three enzymes are present as active forms. In spite of the fact that high levels of gelatinolytic enzymes are present, the major fragmentation products resulting from digestion of intact type I collagen are the 1/4 and 3/4 fragments (products of MMP-1-mediated digestion). Thus, it appears that the gelatinolytic enzymes are not capable of degrading the collagen fragments as rapidly as they are produced. Since previous studies have demonstrated that interaction of interstitial fibroblasts with high molecular weight fragments of type I collagen leads to increased MMP production, the present results suggest a mechanism underlying altered function of stromal elements in the connective tissue adjacent to the growing neoplasm.


Assuntos
Carcinoma Basocelular/enzimologia , Colágeno/metabolismo , Metaloproteinases da Matriz/biossíntese , Fragmentos de Peptídeos/metabolismo , Neoplasias Cutâneas/enzimologia , Western Blotting , Carcinoma Basocelular/patologia , Colágeno/ultraestrutura , Meios de Cultivo Condicionados/metabolismo , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Gelatina/metabolismo , Humanos , Microscopia Eletrônica de Transmissão , Técnicas de Cultura de Órgãos , Neoplasias Cutâneas/patologia
7.
J Invest Dermatol ; 122(6): 1471-9, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15175039

RESUMO

This report provides evidence from a number of different approaches (i.e., comparison of cell shape in 1-microm sections of photodamaged versus healthy skin at the light microscopic level; comparison of cell shape and apposition to collagen fibrils in ultrathin sections of the same tissues examined by transmission electron microscopy, and fluorescence staining for adhesion site protein expression and actin filament architecture in frozen tissue sections) that dermal cells in healthy skin are attached to collagen fibrils over a large part of the cell border, have a flattened/spread (two-dimensional) appearance and have abundant actin in their cytoplasm. In contrast, cells in photodamaged skin are often in contact with fragmented collagen or amorphous debris rather than intact collagen, have a collapsed/elongated shape, and have a lower amount of actin. Collagen synthesis is reduced in severely photodamaged skin relative to collagen synthesis in corresponding sun-protected skin (N Engl J Med 329:530, 1993). We hypothesize that fibroblasts in severely damaged skin have less interaction with intact collagen and as a result experience a reduction in mechanical tension. Decreased collagen synthesis is (presumed to be) the result.


Assuntos
Colágeno/biossíntese , Derme/patologia , Fibroblastos/patologia , Envelhecimento da Pele/patologia , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Biópsia , Adesão Celular , Tamanho Celular , Células Cultivadas , Colágeno/metabolismo , Derme/metabolismo , Derme/efeitos da radiação , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Microscopia Eletrônica , Pessoa de Meia-Idade
8.
J Invest Dermatol ; 120(5): 842-8, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12713591

RESUMO

Biochemical and ultrastructural approaches were used to assess collagen changes in photodamaged skin. Extensive collagen fragmentation, clumping of the fragmented collagen, and interaction of fibroblasts with the damaged matrix were observed. Similar, though less extensive, collagen damage was also observed in sun-protected skin-individuals aged 80 y or older (naturally aged skin). In comparison, sun-protected skin from young individuals (18-29 y of age) demonstrated little damage. A uniform distribution of collagen fibrils was seen. Interstitial fibroblasts were embedded in the collagen matrix and in close apposition with intact collagen fibrils. In additional studies, three-dimensional lattices of type I collagen were exposed in vitro to matrix metalloproteinase-1 (interstitial collagenase), and examined for biochemical and ultrastructural alterations. Under conditions in which enzyme treatment produced fragmentation in 30-40% of the collagen molecules, the lattices demonstrated collagen fragmentation and clumping of the damaged matrix. Recent studies have demonstrated a loss of procollagen production by fibroblasts in contact with collagen fragments in vitro. This study demonstrates similar changes in collagen structure in vivo in aged and photodamaged skin. We suggest that collagen fragmentation in vivo could underlie the loss of collagen synthesis in photodamaged skin and, to a lesser extent perhaps, in aged skin.


Assuntos
Envelhecimento , Colágeno/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Pele/patologia , Pele/efeitos da radiação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biópsia , Humanos , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Ratos , Pele/metabolismo , Pele/ultraestrutura
9.
J Invest Dermatol ; 119(1): 122-9, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12164934

RESUMO

Three-dimensional lattices of reconstituted, polymerized type I collagen were subjected to partial hydrolysis by organ culture fluid from human skin or by various matrix metalloproteinases, including matrix metalloproteinase-1 (interstitial collagenase), -2 (72 kDa gelatinase A), -8 (neutrophil collagenase), -9 (92 kDa gelatinase B), or -13 (collagenase 3). Following partial digestion, human dermal fibroblasts were incubated on the enzyme-treated or control lattices and examined for ability to contract the collagen lattice and synthesize type I procollagen. Collagen lattices partially degraded by organ culture fluid were contracted by fibroblasts under conditions in which control collagen lattices were not. On the partially degraded collagen, fibroblasts synthesized reduced amounts of type I procollagen (approximately 70% reduction). Purified matrix metalloproteinases with collagenolytic activity duplicated the effects of the human skin organ culture fluid, although matrix metalloproteinases 8 and 13 were less efficient than matrix metalloproteinase-1 (65% vs 40% and 18% reduction in type I procollagen production for matrix metalloproteinases 1, 8, and 13, respectively). Matrix metalloproteinases 2 and 9 were without effect on intact collagen; however, when collagen lattices were subjected to digestion by a combination of matrix metalloproteinases 1 and 9, fragments produced by matrix metalloproteinase-1 were further degraded by the gelatinase. Collagen contraction and inhibition of procollagen synthesis were both reduced. Matrix metalloproteinase-2 was less effective than matrix metalloproteinase-9 in clearing matrix metalloproteinase-1-generated fragments. Matrix metalloproteinase-2 was also less effective in preventing contraction and inhibiting the downregulation of type I procollagen synthesis. These observations suggest that in the presence of high molecular weight fragments of type I collagen, type I procollagen synthesis is inhibited. As these fragments are processed further, there is less inhibition of type I procollagen production.


Assuntos
Colágeno Tipo I/biossíntese , Fibroblastos/enzimologia , Envelhecimento da Pele/fisiologia , Tamanho Celular/fisiologia , Colágeno Tipo I/química , Colágeno Tipo I/ultraestrutura , Colagenases/metabolismo , Derme/citologia , Fibroblastos/química , Fibroblastos/ultraestrutura , Humanos , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 13 da Matriz , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Microscopia Eletrônica de Varredura , Peso Molecular , Técnicas de Cultura de Órgãos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo
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