Lipodermatosclerosis is Characterized by Elevated Expression and Activation of Matrix Metalloproteinases: Implications for Venous Ulcer Formation Yared.

Slides:

Advertisements

Similar presentations

Effects of Growth Factors and Basement Membrane Proteins on the Phenotype of U- 373 MG Glioblastoma Cells as Determined by the Expression of Intermediate.

Advertisements

The CXC Receptor 2 Is Overexpressed in Psoriatic Epidermis

Angela Tewari, Katarzyna Grys, Jutta Kollet, Robert Sarkany, Antony R

Skin-Specific Expression of ank-393, a Novel Ankyrin-3 Splice Variant

Matrix Metalloproteinase 9 Expression is Coordinately Modulated by the KRE-M9 and 12-O-Tetradecanoyl-Phorbol-13-Acetate Responsive Elements Takashi Kobayashi,

Pressure distention compared with pharmacologic relaxation in vein grafting upregulates matrix metalloproteinase-2 and -9 Ada W.Y. Chung, PhD, Pooja.

HAX-1, Identified by Differential Display Reverse Transcription Polymerase Chain Reaction, Is Overexpressed in Lesional Psoriasis Alireza Mirmohammadsadegh,

BM-40(Osteonectin, SPARC) Is Expressed Both in the Epidermal and in the Dermal Compartment of Adult Human Skin Nicholas Hunzelmann, Martin Hafner, Sabine.

Zhuo Li, Dieter Metze, Dorothea Nashan, Carsten Müller-Tidow, Hubert L

Interleukin-17 and Interferon-γ Synergize in the Enhancement of Proinflammatory Cytokine Production by Human Keratinocytes Marcel B.M. Teunissen, Jan.

Basement Membrane Zone Remodeling During Appendageal Development in Human Fetal Skin. The Absence of Type VII Collagen is Associated with Gelatinase-A.

Matrix Metalloproteinase-19 Expression in Dermal Wounds and by Fibroblasts in Culture Niina Hieta, Ulla Impola, Carlos López-Otín, Ulpu Saarialho-Kere,

Overexpression of Serpin Squamous Cell Carcinoma Antigens in Psoriatic Skin Atsushi Takeda, Dousei Higuchi, Tadahito Takahashi, Masashi Ogo, Peter Baciu,

Differential Expression of a Novel Gene in Response to hsp27 and Cell Differentiation in Human Keratinocytes Mojgan Hell-Pourmojib, Peter Neuner, Robert.

Differential expression of elastin assembly genes in patients with Stanford Type A aortic dissection using microarray analysis Bernice L.Y. Cheuk, PhD,

Coexpression of Integrin αvβ3 and Matrix Metalloproteinase-2 (MMP-2) Coincides with MMP-2 Activation: Correlation with Melanoma Progression Uta B. Hofmann,

Fibrin and Collagen Differentially Regulate Human Dermal Microvascular Endothelial Cell Integrins: Stabilization of αv/β3 mRNA by Fibrin1 Xiaodong Feng,

Preoperative treatment with doxycycline reduces aortic wall expression and activation of matrix metalloproteinases in patients with abdominal aortic aneurysms

Xu Shi-wen, Christopher P. Denton, Alan M. Holmes, Carol M

Volume 63, Issue 5, Pages (May 2003)

Elastin-Derived Peptides Upregulate Matrix Metalloproteinase-2-ediated Melanoma Cell Invasion Through Elastin-Binding Protein Carole Ntayi, Anne-Laure.

The mRNA for Protease Nexin-1 is Expressed in Human Dermal Papilla Cells and its Level is Affected by Androgen Tadashige Sonoda, Yuji Asada, Sotaro Kurata,

Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms Borhane Annabi, PhD, a, Daniel Shédid, MD, b, Pierre Ghosn,

Membrane Type 1 Matrix Metalloproteinase Regulates Cellular Invasiveness and Survival in Cutaneous Epidermal Cells Usha Nagavarapu, Kenneth Relloma,

Molecular Cloning and Expression of Human Keratinocyte Proline-Rich Protein (hKPRP), an Epidermal Marker Isolated from Calcium-Induced Differentiating.

Differential Expression of Matrix Metalloproteinases During Impaired Wound Healing of the Diabetes Mouse Steven J. Wall, Dr, Damon Bevan, David W. Thomas,

Novel Homozygous and Compound Heterozygous COL17A1 Mutations Associated with Junctional Epidermolysis Bullosa Michaela Floeth, Heike Schäcke, Nadja Hammami-Hauasli,

Modulation of Collagen Metabolism by the Topical Application of Dehydroepiandrosterone to Human Skin Mi Hee Shin, Gi-eun Rhie, Chi-Hyun Park, Kyu Han.

Vitamin A Antagonizes Decreased Cell Growth and Elevated Collagen-Degrading Matrix Metalloproteinases and Stimulates Collagen Accumulation in Naturally.

Protein C Inhibitor is Expressed in Keratinocytes of Human Skin

Characterization of the CC Chemokine Receptor 3 on Human Keratinocytes

Stratifin-Induced Matrix Metalloproteinase-1 in Fibroblast Is Mediated by c-fos and p38 Mitogen-Activated Protein Kinase Activation Eugene Lam, Runhangiz.

Noritaka Oyama, Keiji Iwatsuki, Yoshimi Homma, Fumio Kaneko

Respective Contribution of Neutrophil Elastase and Matrix Metalloproteinase 9 in the Degradation of BP180 (Type XVII Collagen) in Human Bullous Pemphigoid

The Majority of Keratinocytes Incorporate Intradermally Injected Plasmid DNA Regardless of Size but Only a Small Proportion of Cells Can Express the Gene.

Takashi Kobayashi, Hiroshi Shinkai

Expression of T-Cadherin in Basal Keratinocytes of Skin

Regulation of MMP-2 Gene Transcription in Dermal Wounds

The Melanocortin 5 Receptor is Expressed in Human Sebaceous Glands and Rat Preputial Cells Diane Thiboutot, Aruntha Sivarajah, Kathryn Gilliland, Zhaoyuan.

Masahiro Hara, Mina Yaar, H

Role of matrix metalloproteinases 1, 2, and 9 and tissue inhibitor of matrix metalloproteinase-1 in chronic venous insufficiency Satoshi Saito, MD, Matthew.

Eric A.G. Blomme, Charles C. Capen, Thomas J. Rosol

Human Keratinocytes Respond to Osmotic Stress by p38 Map Kinase Regulated Induction of HSP70 and HSP27 M. Garmyn, A. Pupe Journal of Investigative Dermatology

SPARC-Null Mice Display Abnormalities in the Dermis Characterized by Decreased Collagen Fibril Diameter and Reduced Tensile Strength Amy D. Bradshaw,

Keratinocytes Express the CD146 (Muc18/S-Endo) Antigen in Tissue Culture and During Inflammatory Skin Diseases1 Wolfgang Weninger, Michael Rendl, Michael.

Expression and Activation of Matrix Metalloproteinases in Wounds: Modulation by the Tripeptide–Copper Complex Glycyl-L-Histidyl-L-Lysine-Cu2+ Alain Siméon,

Gereon Lauer, Stephan Sollberg, Melanie Cole, Thomas Krieg, Sabine A

Bikunin, a Serine Protease Inhibitor, is Present on the Cell Boundary of Epidermis Cui Chang-Yi, Yoshinori Aragane, Akira Maeda, Piao Yu-Lan, Masae Takahashi,

Expression of Interleukin-12 is Increased in Psoriatic Skin

Akemi Ishida-Yamamoto, Hidetoshi Takahashi, Hajime Iizuka

Matrix Metalloproteinases of Epithelial Origin in Facial Sebum of Patients with Acne and their Regulation by Isotretinoin Eleni Papakonstantinou, Alexios.

Expression of the CD4+ Cell-Specific Chemoattractant Interleukin-16 in Mycosis Fungoides Volker Blaschke, Kristian Reich, Michael Letschert, Florian.

Abnormal Extracellular Matrix Metabolism in Chronically Ischemic Skin: A Mechanism for Dermal Failure in Leg Ulcers Stephen J. Dalton, David C. Mitchell,

Expression of Mast Cell Growth Modulating and Chemotactic Factors and their Receptors in Human Cutaneous Scars Barbara Hermes Journal of Investigative.

Skin Expression of Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Sibling Patients with Recessive Dystrophic Epidermolysis and Intrafamilial.

Expression of FcRn, the MHC Class I-Related Receptor for IgG, in Human Keratinocytes Karla Cauza, Gabriele Hinterhuber, Ruth Dingelmaier-Hovorka, Karin.

Expression of Opsin Molecule in Cultured Murine Melanocyte

Alterations of Glucosylceramide-β-Glucosidase Levels in the Skin of Patients with Psoriasis Vulgaris Francesca Alessandrini, Sabine Pfister, Elisabeth.

Immunoprotective UVA (320–400 nm) Irradiation Upregulates Heme Oxygenase-1 in the Dermis and Epidermis of Hairless Mouse Skin Munif Allanson, Vivienne.

The Level of Prosaposin is Decreased in the Skin of Patients with Psoriasis Vulgaris Francesca Alessandrini, Silke Stachowitz, Johannes Ring, Heidrun.

Venous Leg Ulcers And Apoptosis: A TIMP-3-Mediated Pathway?

Possible Involvement of Gelatinases in Basement Membrane Damage and Wrinkle Formation in Chronically Ultraviolet B-exposed Hairless Mouse Shinji Inomata,

Elevated Matrix Metalloproteinases and Collagen Fragmentation in Photodamaged Human Skin: Impact of Altered Extracellular Matrix Microenvironment on Dermal.

Wanfen Xiong, MD, PhD, Rebecca Knispel, BS, Jason Mactaggart, MD, B

Permeability Barrier Disruption Increases the Level of Serine Palmitoyltransferase in Human Epidermis Francesca Alessandrini, Dr., Heidrun Behrendt

Relationship Between Cell-Associated Matrix Metalloproteinase 9 and Psoriatic Keratinocyte Growth Nathalie Buisson-Legendre, Hervé Emonard, Philippe.

Kristiina Airola, Norbert E. Fusenig

Redistribution of LRIG Proteins in Psoriasis

Effect of Healing on the Expression of Transforming Growth Factor βs and their Receptors in Chronic Venous Leg Ulcers Allison J. Cowin, Nicholas Hatzirodos,

Matrix Metalloproteinase Inhibitor BB-3103 Unlike the Serine Proteinase Inhibitor Aprotinin Abrogates Epidermal Healing of Human Skin Wounds Ex Vivo1

Presentation transcript:

Lipodermatosclerosis is Characterized by Elevated Expression and Activation of Matrix Metalloproteinases: Implications for Venous Ulcer Formation Yared Herouy, Gudula Pornschlegel, Christoph Stetter, Harald Grenz, Erwin Schöpf, Johannes Norgauer, Wolfgang Vanscheidt Journal of Investigative Dermatology Volume 111, Issue 5, Pages 822-827 (November 1998) DOI: 10.1046/j.1523-1747.1998.00369.x Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 The mRNA expression of matrix metalloproteinases and their tissue inhibitors in skin lesions of lipodermatosclerosis. (A) Total mRNA was prepared from biopsy specimen of liposclerotic (left lanes) and healthy skin (right lanes). Reverse transcription and amplification of generated cDNA with polymerase chain reaction was performed. Amplified products of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and the control gene GAPDH were stained by ethidium bromide. Representative data from one patient with lipodermatosclerosis and one control are shown. (B) Densitometric evaluation of generated products of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 from liposclerotic lesions (black bars) and healthy controls (white bars). To compare mRNA expression of different patients, the obtained signals were normalized to the level of the control gene GAPDH by calculating the ratio between the analyzed genes and GAPDH. Data are means ± SEM (n = 6 liposclerotic lesions; n = 6 controls). The significance of difference was determined by an unpaired Student’s t test and is indicated in each mapped group [*p < 0.05, **p < 0.01, ***p < 0.001 and not significant (n.s.)]. Journal of Investigative Dermatology 1998 111, 822-827DOI: (10.1046/j.1523-1747.1998.00369.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Protein expression of matrix metalloproteinases and their tissue inhibitors in extracts of liposclerotic skin lesions. (A, B) Western blot with monoclonal antibodies against MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in liposclerotic skin lesions. A representative immunoblotting from one patient with lipodermatosclerosis and one control are shown. (C, D) Densitometric evaluations of immunoreactive bands for the active and the zymogen form of MMP-1, unbound TIMP-1, and the proMMP-1/TIMP-1 complex as well as for the active and the zymogen form of MMP-2, unbound TIMP-2, and the inactive proMMP-2/TIMP-2 complex from liposclerotic skin (black bars) and healthy skin (white bars). Data are means ± SEM (n = 7 for liposclerotic lesions; n = 6 for controls). The significance of difference was determined by an unpaired Student’s t test and is indicated in each mapped group [*p < 0.05, **p < 0.01, ***p < 0.001 and not significant (n.s.)]. Journal of Investigative Dermatology 1998 111, 822-827DOI: (10.1046/j.1523-1747.1998.00369.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Identification of gelatinolytic proteins in extracts of liposclerotic lesions. (A) SDS-PAGE zymography of extracts from liposclerotic lesions (left lane) and healthy skin (right lane). Equal amounts of total protein were loaded on each lane of a gelatin-containing gel. All tissue extracts displayed gelatinolytic activity comigrating with the zymogen form of MMP-2, proMMP-2, MMP-9, and proMMP-9. Representative data from one patient with lipodermatosclerosis and one control are shown. The experiment was repeated with comparable results. (B) Densitometric evaluation of the gelatinolytic activity of tissue extracts of liposclerotic lesions (back bars) and from healthy skin (white bars). Data are means ± SEM (n = 5 for liposclerotic lesions; n =5 for controls). The significance of difference was determined by an unpaired Student’s t test and is indicated in each mapped group [*p < 0.05, **p < 0.01, ***p < 0.001 and not significant (n.s.)]. Journal of Investigative Dermatology 1998 111, 822-827DOI: (10.1046/j.1523-1747.1998.00369.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Collagen degradation of skin lesions of lipodermatosclerosis. The proteolytic activity of tissue extracts from liposclerotic lesions (black bars) and healthy skin (white bars) was analyzed with [3H]labeled type I collagen and [3H]labeled type IV collagen. Data are means ± SEM (n = 5 for liposclerotic lesions; n = 5 for controls). The significance of difference was determined by an unpaired student’s t test and is indicated in each mapped group (*p < 0.05, **p < 0.01, ***p < 0.001). Journal of Investigative Dermatology 1998 111, 822-827DOI: (10.1046/j.1523-1747.1998.00369.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Immunohistochemical detection of MMP-1, MMP-2, and TIMP-2 in lesions of lipodermatosclerosis. In lipodermatosclerosis MMP-1 displayed increased diffuse immunoreactivity in the epidermis and dermis (A). In contrast MMP-2 was localized in perivascular regions (B), deep reticular dermis (C), and the basal and suprabasal layer of the epidermis (D), whereas in healthy skin diffuse and weak staining pattern was detected. In healthy skin a continuous line of immunoreactivity against TIMP-2 along the basement membrane was found (E), whereas in liposclerotic lesions the signal was weak. Representative photographs from one patient and one control are shown. The experiment was repeated with comparable results (n = 6 for liposclerotic lesions; n = 6 for controls). Scale bars: (A, E) 500 μm; (B) 100 μm; (C) 20 μm; (D) 200 μm. Journal of Investigative Dermatology 1998 111, 822-827DOI: (10.1046/j.1523-1747.1998.00369.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions