The Cutaneous Microfibrillar Apparatus Contains Latent Transforming Growth Factor-β Binding Protein-1 (LTBP-1) and is a Repository for Latent TGF-β1 

Slides:



Advertisements
Similar presentations
Volume 15, Issue 3, Pages (March 2007)
Advertisements

Colocalization of Glial Fibrillary Acidic Protein, Metallothionein, and MHC II in Human, Rat, NOD/SCID, and Nude Mouse Skin Keratinocytes and Fibroblasts 
Possible Involvement of Basement Membrane Damage in Skin Photoaging
Gianni Gerlini, Hans Peter Hefti, Martin Kleinhans, Brian J
Epstein–Barr Virus Infection Induces Aberrant TLR Activation Pathway and Fibroblast– Myofibroblast Conversion in Scleroderma  Antonella Farina, Mara Cirone,
Hee-Young Park, PhD, Jin Lee, Sameer Kapasi, Shaun Peterson, Barbara A
Expression and Role of IL-15 in Post-Burn Hypertrophic Scars
Transient Bullous Dermolysis of the Newborn Associated with Compound Heterozygosity for Recessive and Dominant COL7A1 Mutations  Nadja Hammami-Hauasli,
Peroxiredoxin is Ubiquitously Expressed in Rat Skin: Isotype-Specific Expression in the Epidermis and Hair Follicle  Jeong Eun Lee, Byung Dae Kwon, Jee-Bum.
The Autoantigen in Anti-p200 Pemphigoid Is Synthesized by Keratinocytes and Fibroblasts and Is Distinct from Nidogen-2  Silke C. Hofmann, Ursula Voith,
BM-40(Osteonectin, SPARC) Is Expressed Both in the Epidermal and in the Dermal Compartment of Adult Human Skin  Nicholas Hunzelmann, Martin Hafner, Sabine.
Focal Dermal–Epidermal Separation and Fibronectin Cleavage in Basement Membrane by Human Mast Cell Tryptase  Renata Kaminska, Petra Helisalmi, Rauno J.
John E. Olerud, Diane S. Chiu, Marcia L. Usui 
Activation-Dependent Modulation of Hyaluronate-Receptor Expression and of Hyaluronate-Avidity by Human Monocytes  Johannes M. Weiss, Andreas C. Renkl,
Expression of Type XVI Collagen in Human Skin Fibroblasts: Enhanced Expression in Fibrotic Skin Diseases  Atsushi Akagi, Shingo Tajima, Yutaka Nagai 
Pathogenic Epitopes of Autoantibodies in Pemphigus Reside in the Amino-Terminal Adhesive Region of Desmogleins Which Are Unmasked by Proteolytic Processing.
Basement Membrane Zone Remodeling During Appendageal Development in Human Fetal Skin. The Absence of Type VII Collagen is Associated with Gelatinase-A.
Connexins 26, 30, and 43: Differences Among Spontaneous, Chronic, and Accelerated Human Wound Healing  Johanna M. Brandner, Pia Houdek, Birgit Hüsing,
Heme-Scavenging Role of α1-Microglobulin in Chronic Ulcers
Ahmad Waseem, Yasmin Alam, Anand Lalli 
Expression of Multiple Cytochrome P450 Enzymes and Multidrug Resistance- Associated Transport Proteins in Human Skin Keratinocytes  Jens M. Baron, Daniela.
Upregulation of Tumor Suppressor Protein Neurofibromin in Normal Human Wound Healing and In Vitro Evidence for Platelet Derived Growth Factor (PDGF) and.
Ellen A. Rorke, Gautam Adhikary, Christina A. Young, Dennis R
Ann-Marie Broome, Richard L. Eckert, PhD 
Localization of Calcineurin/NFAT in Human Skin and Psoriasis and Inhibition of Calcineurin/NFAT Activation in Human Keratinocytes by Cyclosporin A  Wael.
Isoforms and splice variant of transforming growth factor β–binding protein in rat hepatic stellate cells  Wenrong Gong, Sylke Roth, Kristin Michel, Axel.
Colocalization of Kindlin-1, Kindlin-2, and Migfilin at Keratinocyte Focal Adhesion and Relevance to the Pathophysiology of Kindler Syndrome  J.E. Lai-Cheong,
Marie-Thérèse Leccia  Journal of Investigative Dermatology 
Autoimmunity: Alopecia Areata
Epithelial Cells Promote Fibroblast Activation via IL-1α in Systemic Sclerosis  Nima Aden, Anna Nuttall, Xu Shiwen, Patricia de Winter, Andrew Leask, Carol.
Katrin Pauls, Margarete Schön, Robert C
Assembly of Epithelial Cell Fibrillins
S100A7 (Psoriasin) Interacts with Epidermal Fatty Acid Binding Protein and Localizes in Focal Adhesion-Like Structures in Cultured Keratinocytes  Monica.
Inhibition of Hair Follicle Growth by a Laminin-1 G-Domain Peptide, RKRLQVQLSIRT, in an Organ Culture of Isolated Vibrissa Rudiment1  Kazuhiro Hayashi,
A TGF-β1-Dependent Autocrine Loop Regulates the Structure of Focal Adhesions in Hypertrophic Scar Fibroblasts  Ganary Dabiri, Anelisa Campaner, Jeffrey.
Light and Electron Microscopic Demonstration of the p75 Nerve Growth Factor Receptor in Normal Human Cutaneous Nerve Fibers: New Vistas  Yong Liang, Olle.
Protein Phosphatase Type 1-Dependent Dephosphorylation of the Retinoblastoma Tumor Suppressor Protein in Ultraviolet-Irradiated Human Skin and Keratinocytes 
Sustained Activation of Fibroblast Transforming Growth Factor-β/Smad Signaling in a Murine Model of Scleroderma  Shinsuke Takagawa, Gabriella Lakos, Yasuji.
Ultraviolet B Irradiation Induces Expansion of Intraepithelial Tumor Cells in a Tissue Model of Early Cancer Progression  Norbert E. Fusenig  Journal.
Expression of Matrilin-2 in Human Skin
Organotypic Cocultures with Genetically Modified Mouse Fibroblasts as a Tool to Dissect Molecular Mechanisms Regulating Keratinocyte Growth and Differentiation 
Mutant Loricrin is Not Crosslinked into the Cornified Cell Envelope but is Translocated into the Nucleus in Loricrin Keratoderma  Akemi Ishida-Yamamoto,
Normal and Gene-Corrected Dystrophic Epidermolysis Bullosa Fibroblasts Alone Can Produce Type VII Collagen at the Basement Membrane Zone  David T. Woodley,
Keratinocytes Influence the Maturation and Organization of the Elastin Network in a Skin Equivalent1  Florence Duplan-Perrat, Odile Damour, Caroline Montrocher,
Expression of T-Cadherin in Basal Keratinocytes of Skin
The Hyaluronan Synthesis Inhibitor 4-Methylumbelliferone Prevents Keratinocyte Activation and Epidermal Hyperproliferation Induced by Epidermal Growth.
Trangenic Misexpression of the Differentiation-Specific Desmocollin Isoform 1 in Basal Keratinocytes  Frank Henkler, Molly Strom, Kathleen Mathers, Hayley.
Inhibition of the Transforming Growth Factor-β/Smad Signaling Pathway in the Epithelium of Oral Lichen  Andreas Karatsaidis, Olav Schreurs, Kristen Helgeland,
Prevalence of Antibodies Against Virus-Like Particles of Epidermodysplasia Verruciformis-Associated HPV8 in Patients at Risk of Skin Cancer  Sabine Stark,
Versican, a Major Hyaluronan-Binding Component in the Dermis, Loses its Hyaluronan- Binding Ability in Solar Elastosis  Keiko Hasegawa, Masahiko Yoneda,
SPARC-Null Mice Display Abnormalities in the Dermis Characterized by Decreased Collagen Fibril Diameter and Reduced Tensile Strength  Amy D. Bradshaw,
Molecular Consequences of Deletion of the Cytoplasmic Domain of Bullous Pemphigoid 180 in a Patient with Predominant Features of Epidermolysis Bullosa.
Basal-Cell Adhesion Molecule (B-CAM) is Induced in Epithelial Skin Tumors and Inflammatory Epidermis, and is Expressed at Cell–Cell and Cell–Substrate.
Mitogen- and Stress-Activated Protein Kinase 2 and Cyclic AMP Response Element Binding Protein are Activated in Lesional Psoriatic Epidermis  Anne T.
Akemi Ishida-Yamamoto, Hidetoshi Takahashi, Hajime Iizuka 
Matrix Metalloproteinases in Human Melanoma
Serum IgE Autoantibodies Target Keratinocytes in Patients with Atopic Dermatitis  Sabine Altrichter, Ernst Kriehuber, Julia Moser, Rudolf Valenta, Tamara.
Apolipoprotein E is Present in Primary Localized Cutaneous Amyloidosis
IgG Autoantibodies from Bullous Pemphigoid (BP) Patients Bind Antigenic Sites on Both the Extracellular and the Intracellular Domains of the BP Antigen.
The Expression of Vitamin D-Upregulated Protein 1 in Skin and its Interaction with Sciellin in Cultured Keratinocytes  Marie-France Champliaud, Alain.
Expression of FcRn, the MHC Class I-Related Receptor for IgG, in Human Keratinocytes  Karla Cauza, Gabriele Hinterhuber, Ruth Dingelmaier-Hovorka, Karin.
Elafin, a Secretory Protein, is Cross-Linked into the Cornified Cell Envelopes from the Inside of Psoriatic Keratinocytes  Hiroshi Nakane, Akemi Ishida-Yamamoto,
Thilo Jakob, Mark C. Udey  Journal of Investigative Dermatology 
The TGFβ large latent complex (LLC).
Mariangela Marques, Yong Pei, Michael D. Southall, John M
The Relaxin Gene Knockout Mouse: A Model of Progressive Scleroderma
Y. Albert Pan, Joshua R. Sanes  Journal of Investigative Dermatology 
Characterization of a Composite Tissue Model that Supports Clonal Growth of Human Melanocytes In Vitro and In Vivo  Daniel A. Medalie, Ronald G. Tompkins,
Fibroblast Growth Factor 10 Induces Proliferation and Differentiation of Human Primary Cultured Keratinocytes  Cinzia Marchese, Alessandra Felici, Vincenzo.
Matrix Metalloproteinase Inhibitor BB-3103 Unlike the Serine Proteinase Inhibitor Aprotinin Abrogates Epidermal Healing of Human Skin Wounds Ex Vivo1 
Presentation transcript:

The Cutaneous Microfibrillar Apparatus Contains Latent Transforming Growth Factor-β Binding Protein-1 (LTBP-1) and is a Repository for Latent TGF-β1  Michael Raghunath, Christine Unsöld, Leena Bruckner-Tuderman  Journal of Investigative Dermatology  Volume 111, Issue 4, Pages 559-564 (October 1998) DOI: 10.1046/j.1523-1747.1998.00339.x Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Immunoblot and radioimmunoprecipitation analyses exclude cross-reactivity of Ab39 against LTBP-1 with fibrillin. (a) Immunoblot from proteins from conditioned fibroblast culture medium separated on a 4% sodium dodecyl sulfate-polyacrylamide gel under nonreducing conditions and transferred onto nitrocellulose. Immunodetection of LTBP-1 with Ab39 results in a broad double band at ≈200kDa (lane 1), whereas MoAb69 recognizes only fibrillin migrating at ≈320kDa (lane 2). Fibrillin is not recognized by Ab39 (lane 1) nor is LTBP-1 recognized by Ab39. (b) Ab39 immunoprecipitates LTPB-1 as a 200kDa protein from culture medium of metabolically labeled fibroblasts. There is no coprecipitation of fibrillin. Lane 1, normal rabbit serum;lane 2, fibronectin;lane 3, LBTP-1;lane 4, crude medium Journal of Investigative Dermatology 1998 111, 559-564DOI: (10.1046/j.1523-1747.1998.00339.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 LTBP-1 is a constituent of the microfibrillar apparatus of the skin. Confocal laser scanning localization of fibrillin and LTBP-1 in normal and regenerating skin. Each micrograph represents an extended focus view calculated from 10 section planes (increment 0.360 μm). The yellow mix color of superimposed images obtained for LTBP-1 (green immunofluorescence) and fibrillin (red immunofluorescence) suggests in normal skin extensive colocalization of fibrillin and LTBP-1 on the transpapillary (a) and the reticular portion of the microfibrillar apparatus (b). Regenerating skin: extensive colocalization of LTBP-1 with fibrillin throughout all developmental stages of the microfibrillar apparatus from day 7 after grafting (c), 1 mo after grafting (d), 17 mo after grafting (e), and 2 y after grafting (f). Scale bar: 10 μm. Journal of Investigative Dermatology 1998 111, 559-564DOI: (10.1046/j.1523-1747.1998.00339.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Microfibrils of different tissues are a repository for latent TGF-β1. Confocal laser scanning study of fibrillin and TGF-β1 precursor on microfibrillar structures in human skin and cynomolgus monkey eye. (a–c) Tissues were double stained with MoAb69 against fibrillin (red signal) and anti-β-LAP (green signal). (a, b) The yellow mix color of superimposed images demonstrates association of TGF-β1 precursor with fibrillin-microfibrils. Note that the cytoplasm of basal and suprabasal keratinocytes contains latent TGF-β1. (c) Eye: the picture shows a rod-like ciliary zonule as part of the suspensory ligament of the eye lens surrounded by parts of the iris and the processus ciliaris. The yellow mix color demonstrates colocalization of fibrillin and latent TGF-β1 on the ciliary zonule fiber. (d) Human papillary dermis simultaneously immunostained for fibrillin (blue signal), LTBP-1 (green signal), and TGF-β1 precursor (red signal). The white mix colors indicates colocalization of all three antigens on individual microfibrillar bundles. Scale bars: 10 μm. Journal of Investigative Dermatology 1998 111, 559-564DOI: (10.1046/j.1523-1747.1998.00339.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Fibrillin but not LBTP-1 is present on zonule fibrils of the cynomolgus monkey eye. Conventional immunofluorescence detection of fibrillin (a) and LTBP-1 (b) in equatorial cryosection sections of cynomolgus monkey eye. L, lens; C, lens capsule; ZF, zonule fibril. Fibrillin is present on zonule fibrils, whereas LTBP-1 cannot be detected. Scale bars: 25 μm. Journal of Investigative Dermatology 1998 111, 559-564DOI: (10.1046/j.1523-1747.1998.00339.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 The developing microfibrillar apparatus is capable of latent TGF-β1 storage. Confocal laser scanning localization of fibrillin and TGF-β1 precursor in regenerating skin. Tissues were double stained with MoAb69 against fibrillin (red immunofluorescence) and anti-β-LAP (green immunofluorescence). The yellow mix color of superimposed images demonstrates association of latent TGF-β1 with fibrillin-microfibrils: (a) 7 d after keratinocyte grafting; (b) 1 mo after keratinocyte grafting; (c and d) 17 mo after keratinocyte grafting; (d) represents a high power view of the region designated by the square in (c). (e) Papillary dermis after 24 mo; (f) deep reticular dermis after 24 mo. There is discordant distribution of both antigens on blood vessels (e) and m. arrector pili which are positive for latent TGF-β1 only. Scale bar: 10 μm. Journal of Investigative Dermatology 1998 111, 559-564DOI: (10.1046/j.1523-1747.1998.00339.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Plasmin removes β-LAP from cutaneous microfibrils. Cryosections of normal human skin were immunostained for TGF-β1 precursor. (a) Untreated epidermis and papillary dermis; (c) untreated reticular dermis and a m. arrector pili; (b) cryosections treated with 0.1 U plasmin per ml for 1h prior to immunostaining; (d) comparable region of the reticular dermis after plasmin treatment; (e, f) fibrillin staining confirms absence of conspicuous damage to the microfibrillar apparatus by plasmin. Scale bars: 50 μm. Journal of Investigative Dermatology 1998 111, 559-564DOI: (10.1046/j.1523-1747.1998.00339.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 7 Schematic drawing of microfibril-associated latent TGF-β1. Small latent TGF-β is composed of TGF-β dimer bound noncovalently to its prodomain dimer (β-LAP). Large latent TGF-β is formed from small latent TGF-β and LTBP. LTBP associates with β-LAP by a disulfide bond, and to microfibrils via an unknown mechanism (Nunes et al. 1997). A proteinase-sensitive hinge in LTBP beween the contact region with the ECM and the TGF-β binding domains is highlighted. Cleavage at this protease-sensitive region results in the release of latent TGF-β from microfibrils, whereas the cleavage of β-LAP results in the generation of active TGF-β (modified fromSaharinen et al. 1996). Journal of Investigative Dermatology 1998 111, 559-564DOI: (10.1046/j.1523-1747.1998.00339.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions