Mechanisms of Hypoxic Regulation of Plasminogen Activator Inhibitor-1 Gene Expression in Keloid Fibroblasts Qunzhou Zhang, Yidi Wu, David K. Ann, Diana.

Slides:

Advertisements

Similar presentations

IL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway Hee Jung Kim, Seok Bean Song, Jung Min Choi, Kyung Moon Kim,

Advertisements

Oxysterols Induce Differentiation in Human Keratinocytes and Increase Ap-1-Dependent Involucrin Transcription Karen Hanley, Dean C. Ng, ShanShan He,

UVB Increases Urokinase-Type Plasminogen Activator Receptor (uPAR) Expression1 Christoph Marschall, Toshiko Nobutoh, Evelyn Braungart, Kathrin Douwes,

NF-κB Accumulation Associated with COL1A1 Transactivators Defects during Chronological Aging Represses Type I Collagen Expression through a –112/–61-bp.

Differential Regulation by IL-1β and EGF of Expression of Three Different Hyaluronan Synthases in Oral Mucosal Epithelial Cells and Fibroblasts and Dermal.

Constitutive Phosphorylation of Focal Adhesion Kinase Is Involved in the Myofibroblast Differentiation of Scleroderma Fibroblasts Yoshihiro Mimura, Hironobu.

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

Role of hypoxia-inducible factor-1 alpha in the regulation of plasminogen activator activity in rat knee joint chondrocytes G. Zhu, Y. Tang, X. Liang,

Blocking Sp1 Transcription Factor Broadly Inhibits Extracellular Matrix Gene Expression In Vitro and In Vivo: Implications for the Treatment of Tissue.

Julie M. Caldwell, PhD, Carine Blanchard, PhD, Margaret H

Volume 133, Issue 6, Pages (December 2007)

Increased KGF Expression Promotes Fibroblast Activation in a Double Paracrine Manner Resulting in Cutaneous Fibrosis Johanna Canady, Stephanie Arndt,

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

Epidermal Growth Factor Induces Fibronectin Expression in Human Dermal Fibroblasts via Protein Kinase C δ Signaling Pathway Yoshihiro Mimura, Hironobu.

Insulin-Like Growth Factor-I Enhances Transforming Growth Factor-β-Induced Extracellular Matrix Protein Production Through the P38/Activating Transcription.

Naoko Kanda, Shinichi Watanabe Journal of Investigative Dermatology

IFN-γ Upregulates Expression of the Mouse Complement C1rA Gene in Keratinocytes via IFN-Regulatory Factor-1 Sung June Byun, Ik-Soo Jeon, Hyangkyu Lee,

Peter Schroeder, Juergen Lademann, Maxim E

Modulation of the expression of tissue plasminogen activator and its inhibitor by hypoxia in human peritoneal and adhesion fibroblasts Ghassan M Saed,

Volume 12, Issue 3, Pages (July 2015)

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

Green Tea Extract and (−)-Epigallocatechin-3-Gallate Inhibit Mast Cell-Stimulated Type I Collagen Expression in Keloid Fibroblasts via Blocking PI-3K/Akt.

Transcriptional activation of transforming growth factor-β1 in mesangial cell culture by high glucose concentration Brenda B. Hoffman, Kumar Sharma,

Pseudomonas Aeruginosa- and IL-1β-Mediated Induction of Human β-Defensin-2 in Keratinocytes Is Controlled by NF-κB and AP-1 Kai Wehkamp, Lars Schwichtenberg,

Andreea M. Bujor, Jaspreet Pannu, Shizhong Bu, Edwin A. Smith, Robin C

IGF-II-Mediated COX-2 Gene Expression in Human Keratinocytes Through Extracellular Signal-Regulated Kinase Pathway Hye Jung Kim, Tae-Yoon Kim Journal.

Tomoyasu Hattori, Lukasz Stawski, Sashidhar S

An Autocrine Loop Mediates Expression of Vascular Endothelial Growth Factor in Human Dermal Microvascular Endothelial Cells Barbara Vega-Diaz, Serge.

Role of p38 MAPK in Transforming Growth Factor β Stimulation of Collagen Production by Scleroderma and Healthy Dermal Fibroblasts Madoka Sato, Daniel.

Volume 129, Issue 5, Pages (November 2005)

Sang-Wahn Koo, Katherine A. Casper, Kristen B. Otto, Amy K

Prolonged Activation of ERK Contributes to the Photorejuvenation Effect in Photodynamic Therapy in Human Dermal Fibroblasts Yong Hyun Jang, Gi-Bang Koo,

Volume 57, Issue 4, Pages (April 2000)

Regulation of renal proximal tubular epithelial cell hyaluronan generation: Implications for diabetic nephropathy Stuart Jones, Suzanne Jones, Aled Owain.

Histamine Enhances the Production of Granulocyte-Macrophage Colony-Stimulating Factor via Protein Kinase Cα and Extracellular Signal-Regulated Kinase.

Upregulation of Tenascin-C Expression by IL-13 in Human Dermal Fibroblasts via the Phosphoinositide 3-kinase/Akt and the Protein Kinase C Signaling Pathways

Histamine Inhibits the Production of Interferon-induced Protein of 10 kDa in Human Squamous Cell Carcinoma and Melanoma Naoko Kanda, Shinichi Watanabe

Functional Characterization of IL-17F as a Selective Neutrophil Attractant in Psoriasis Hideaki Watanabe, Mio Kawaguchi, Sawa Fujishima, Miyoko Ogura,

Volume 136, Issue 3, Pages (March 2009)

Cyclooxygenase-2 Inhibitor Enhances Whereas Prostaglandin E2Inhibits the Production of Interferon-Induced Protein of 10 kDa in Epidermoid Carcinoma A431

Halofuginone, an Inhibitor of Type-I Collagen Synthesis and Skin Sclerosis, Blocks Transforming-Growth-Factor-β-Mediated Smad3 Activation in Fibroblasts

Reduced Expression of Connective Tissue Growth Factor (CTGF/CCN2) Mediates Collagen Loss in Chronologically Aged Human Skin TaiHao Quan, Yuan Shao, Tianyuan.

TNF-α Suppresses α-Smooth Muscle Actin Expression in Human Dermal Fibroblasts: An Implication for Abnormal Wound Healing Mytien T. Goldberg, Yuan-Ping.

UVB and Proinflammatory Cytokines Synergistically Activate TNF-α Production in Keratinocytes through Enhanced Gene Transcription Muhammad M. Bashir,

Lori Wilson, Csaba Szabó, Andrew L. Salzman Gastroenterology

IL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway Hee Jung Kim, Seok Bean Song, Jung Min Choi, Kyung Moon Kim,

BMP-4 Upregulates Kit Expression in Mouse Melanoblasts prior to the Kit-Dependent Cycle of Melanogenesis Tamihiro Kawakami, Satoko Kimura, Yoko Kawa,

Collagen Synthesis Is Suppressed in Dermal Fibroblasts by the Human Antimicrobial Peptide LL-37 Hyun Jeong Park, Dae Ho Cho, Hee Jung Kim, Jun Young.

Regulation of Guanylate-Binding Protein Expression in Interferon-γ-Treated Human Epidermal Keratinocytes and Squamous Cell Carcinoma Cells Nicholas A.

Jens Gaedeke, Nancy A. Noble, Wayne A. Border Kidney International

17β-Estradiol Inhibits Oxidative Stress-Induced Apoptosis in Keratinocytes by Promoting Bcl-2 Expression Naoko Kanda, Shinichi Watanabe Journal of Investigative.

Fan Yang, Huafeng Zhang, Yide Mei, Mian Wu Molecular Cell

Post-Transcriptional Regulation of UV Induced TNF-α Expression

Volume 70, Issue 5, Pages (September 2006)

Transient Receptor Potential Vanilloid-1 Mediates Heat-Shock-Induced Matrix Metalloproteinase-1 Expression in Human Epidermal Keratinocytes Wen H. Li,

Suppression of VEGFR2 Expression in Human Endothelial Cells by Dimethylfumarate Treatment: Evidence for Anti-Angiogenic Action Markus Meissner, Monika.

Regulation of Tissue Factor in Microvascular Dermal Endothelial Cells

Volume 55, Issue 2, Pages (February 1999)

John M. Lamar, Vandana Iyer, C. Michael DiPersio

All-Trans Retinoic Acid Antagonizes UV-Induced VEGF Production and Angiogenesis via the Inhibition of ERK Activation in Human Skin Keratinocytes Mi-Sun.

Involvement of PPARγ in Oxidative Stress-Mediated Prostaglandin E2 Production in SZ95 Human Sebaceous Gland Cells Qiwei Zhang, Holger Seltmann, Christos.

Kristiina Airola, Norbert E. Fusenig

Volume 11, Issue 1, Pages (January 2005)

IL-12 Completely Blocks Ultraviolet-Induced Secretion of Tumor Necrosis Factor α from Cultured Skin Fibroblasts and Keratinocytes Victoria P. Werth,

Bcl-2 and bcl-xL Antisense Oligonucleotides Induce Apoptosis in Melanoma Cells of Different Clinical Stages Robert A. Olie, Christoph Hafner, Renzo Küttel,

Induction of Interferon Regulatory Factor 1 Expression in Human Dermal Endothelial Cells by Interferon-γ and Tumor Necrosis Factor-α Is Transcriptionally.

Hepatocyte Growth Factor/Scatter Factor (HGF/SF) Induces Vascular Permeability Factor (VPF/VEGF) Expression by Cultured Keratinocytes Jens Gille, Mona.

Increased Migration of Murine Keratinocytes Under Hypoxia Is Mediated by Induction of Urokinase Plasminogen Activator Richard J. Daniel, Richard W. Groves,

Suppression of Keratinocyte Growth and Differentiation by Transforming Growth Factor β1 Involves Multiple Signaling Pathways Alison L. Dahler, Lois L.

Heparin-Binding EGF-Like Growth Factor Is Induced by Disruption of Lipid Rafts and Oxidative Stress in Keratinocytes and Participates in the Epidermal.

Presentation transcript:

Mechanisms of Hypoxic Regulation of Plasminogen Activator Inhibitor-1 Gene Expression in Keloid Fibroblasts Qunzhou Zhang, Yidi Wu, David K. Ann, Diana V. Messadi, Tai-Lan Tuan, A. Paul Kelly, Charles N. Bertolami, Anh D. Le Journal of Investigative Dermatology Volume 121, Issue 5, Pages 1005-1012 (November 2003) DOI: 10.1046/j.1523-1747.2003.12564.x Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Keloid tissues and fibroblasts express higher levels of PAI-1 and HIF-1α than normal skins. (A) Western blot analyses of PAI-1 and HIF-1α proteins present in tissue homogenates obtained from three representative sets of keloid lesions (K1, K2, K3) and associated clinically normal peripheral skins (N1, N2, N3); N1 and K1 were obtained from the same patient and likewise for N2, K2 or N3, K3. (B) Northern blot analyses of PAI-1 mRNAs using dermal fibroblasts isolated from the corresponding keloid tissues and associated normal skin borders. Journal of Investigative Dermatology 2003 121, 1005-1012DOI: (10.1046/j.1523-1747.2003.12564.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Effect of hypoxia on PAI-1 mRNA stability in primary cultured dermal fibroblasts. Northern blot analyses of PAI-1 mRNA half-life of normal skin fibroblasts (B,F) or keloid fibroblasts (A,E) exposed to normoxia (20% O2), intracellular hypoxia (DFO, 130 μmol/L) or environmental hypoxia (2% O2) for 24 h. (C,D,G,H) Densitometric analyses of the 3.2-kb PAI-1 mRNAs with the PAI-1 mRNA/β-actin ratio at time point 0 h arbitrarily set as 1.0. Journal of Investigative Dermatology 2003 121, 1005-1012DOI: (10.1046/j.1523-1747.2003.12564.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Effect of cycloheximide on DFO-induction of PAI-1 mRNA expression in cultured keloid fibroblasts. (A) Northern blot analysis of PAI-1 mRNA following treatment with DFO or CHX. Lane 1, control; lane 2, incubation with CHX (10 μg/mL) for 26 h; lane 3, treatment with DFO (130 μmol/L) for 24 h; and lane 4, following pretreatment with CHX for 2 h, cells were further incubated with DFO for 24 h. (B) Densitometric analysis of the 3.2-kb PAI-1 mRNAs. Journal of Investigative Dermatology 2003 121, 1005-1012DOI: (10.1046/j.1523-1747.2003.12564.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Effect of cycloheximide and actinomycin D on hypoxia upregulation of PAI-1 mRNA expressions in cultured keloid fibroblasts. (A) Northern blot analyses of PAI-1 mRNA following different treatments. Lane 1, control; lane 2, exposure to hypoxia (2% O2) for 24 h (hyp); lane 3, incubation with actinomycin D alone (act. D; 5 μg/mL) for 26 h; lane 4, following pretreatment with actinomycin D for 2 h, cells were exposed to hypoxia for 24 h; lane 5, incubation with CHX (10 μg/mL) alone for 26 h; lane 6, following pretreatment with CHX for 2 h, cells were exposed to hypoxia for another 24 h. (B) Densitometric analysis of the 3.2-kb PAI-1 mRNAs. Journal of Investigative Dermatology 2003 121, 1005-1012DOI: (10.1046/j.1523-1747.2003.12564.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Hypoxia-induced activation of PAI-1 promoter is dependent on de novo protein synthesis. Semiconfluent cultures of keloid fibroblasts were transiently transfected with the pGL3PAI-800Luc construct and exposed to different treatment conditions-including environmental hypoxia (hyp; 2% O2), DFO (130 μmol/L), or CHX (10 μg/mL). The relative activities of the luciferase reporter genes were assayed. Each column represents the mean±SEM (n=3) for three separate experiments. Journal of Investigative Dermatology 2003 121, 1005-1012DOI: (10.1046/j.1523-1747.2003.12564.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Blocking of HIF-1α mRNA expression by antisense oligonucleotides. (A) Keloid fibroblasts were transfected with HIF-1α sense (S) and antisense oligonucleotides (AS), exposed to normoxia or hypoxia for 48 h, and total RNAs were extracted for determination of HIF-1α and α-actin expression by RT-PCR. (B) Ratio of HIF-1α to α-actin band densities of PCR products. The result is representative of three independent experiments. Journal of Investigative Dermatology 2003 121, 1005-1012DOI: (10.1046/j.1523-1747.2003.12564.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 7 Effect of HIF-1α depletion on PAI-1 gene expression in keloid fibroblasts. (A) The HIF-1α sense (S) and antisense (AS) transfected cells were exposed to normoxia or hypoxia for 48 h and total RNAs were extracted for determination of PAI-1 and α-actin expression by RT-PCR. (B) Ratio of PAI-1 band densities to α-actin of PCR products. The result is representative of three independent experiments. Journal of Investigative Dermatology 2003 121, 1005-1012DOI: (10.1046/j.1523-1747.2003.12564.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions