Connective Tissue Growth Factor Gene Expression in Tissue Sections From Localized Scleroderma, Keloid, and Other Fibrotic Skin Disorders

Connective tissue growth factor (CTGF) is a novel peptide that exhibits platelet-derived growth factor-like activities and is produced by skin fibroblasts after activation with transforming growth factor-β. Coordinate expression of transforming growth factor-β followed by CTGF during wound repair suggests a cascade process for control of tissue regeneration. We recently reported a significant correlation between CTGF mRNA expression and histologic sclerosis in systemic sclerosis. To confirm the relation between CTGF and skin fibrosis, we investigated CTGF gene expression in tissue sections from patients with localized scleroderma, keloid, and other sclerotic skin disorders using nonradioactive in situ hybridization. In localized scleroderma, the fibroblasts with positive signals for CTGF mRNA were scattered throughout the sclerotic lesions with no preferential distribution around the inflammatory cells or perivascular regions, whereas the adjacent nonaffected dermis was negative for CTGF mRNA. In keloid tissue, the fibroblasts positive for CTGF mRNA were diffusely distributed, especially in the peripheral expanding lesions. In scar tissue, however, the fibroblasts in the fibrotic lesions showed partially positive signals for CTGF mRNA. In eosinophilic fasciitis, nodular fasciitis, and Dupuytren's contracture, CTGF mRNA was also expressed partially in the fibroblasts of the fibrotic lesions. Our findings reinforce a correlation between CTGF gene expression and skin sclerosis and support the hypothesis that transforming growth factor-β plays an important role in the pathogenesis of fibrosis, as it is the only inducer for CTGF identified to date

Spontaneous Expression of the c-sis Gene and Release of a Platelet-derived Growth Factorlike Molecule by Human Alveolar Macrophages

Alveolar macrophages from normal individuals and patients with interstitial lung diseases spontaneously expressed a 4.2-kilobase mRNA complementary to the c-sis gene, a proto-oncogene coding for one of the chains of platelet-derived growth factor (PDGF). Concomitantly, these cells released a mediator with the properties of PDGF, including: (a) chemotactic factor for smooth muscle cells whose activity was resistant to heat and acid, but sensitive to reduction; (b) mitogenic (competence) activity for fibroblasts; (c) ability to compete with PDGF for its receptor, and (d) precipitated by an anti-PDGF antibody. While blood monocytes did not contain c-sis mRNA transcripts, monocytes matured in vitro expressed c-sis, consistent with the concept that expression of c-sis occurs during the differentiation of monocytes into alveolar macrophages. Together with the known actions of PDGF, these observations suggest that the c-sis proto-oncogene and its PDGF product are part of the armamentarium available to the alveolar macrophages for normal lung defense and participation in lung inflammation

Methods and uses of connective tissue growth factor for differentiation of mesenchymal stem cells

The present invention relates to novel methods and compositions related to the administration of connective tissue growth factor, alone or in combination with other growth factors, compositions or compounds, to induce the differentiation of mesenchymal stem cells into chondrocytes or asteablasts

Leukocyte derived growth factor 2

A protein, Leukocyte Derived Growth Factor 2 (hereinafter LDGF2) having PDGF-like activity is described. LDGF2 reacts with PDGF receptors and possesses mitogenic and/or chemotactic activity for various cell types, particularly connective tissue cells. LDGF2 may be used as the active ingredient in therapeutic compositions, e.g. wound healing compositions, or even further may be used as an additive to cell culture media for the purpose of stimulating cell growth. The protein has a molecular weight of about 7000 daltons determined by SDS gel electrophoresis and is about 61 amino acids in length

Connective tissue growth factor (CTGF) regulatory nucleic acid sequences

The present invention provides a novel polypeptide, Connective Tissue Growth Factor (CTGF), polynucleotides encoding CTGF, and including 5\u27 and 3\u27 untranslated nucleotides, antibodies reactive with CTGF and means for producing CTGF. Also provided are diagnostic and therapeutic methods for using CTGF, as well as an assay for identifying compositions which affect the expression of CTGF polynucleotide. The invention provides a novel TGF-.beta. responsive element upstream of the polynucleotide encoding CTGF structural gene

Connective tissue growth factor

The present invention provides a novel polypeptide, Connective Tissue Growth Factor (CTGF), polynucleotides encoding CTGF and polynucleotides regulating CTGF expression. The invention also provides agents that modulate CTGF and therapeutic methods for using the agents. Also provided are diagnostic methods for using CTGF and assays for identifying agents which affect the expression of CTGF polynucleotide

Methods of identifying a composition that alters connective tissue growth factor expression

The present invention provides a novel polypeptide, Connective Tissue Growth Factor (CTGF), polynucleotides encoding CTGF, and including 5\u27 and 3\u27 untranslated nucleotides, antibodies reactive with CTGF and means for producing CTGF. Also provided are diagnostic and therapeutic methods for using CTGF, as well as an assay for identifying compositions which affect the expression of CTGF polynucleotide. The invention provides a novel TGF-.beta. responsive element upstream of the polynucleotide encoding CTGF structural gene

Methods of accelerating wound healing or of stimulating connective tissue cell growth using connective tissue growth factor

Connective Tissue Growth Factor (CTGF), means for producing CTGF, as well as diagnostic and therapeutic methods for using CTGF

Connective tissue growth factor

The present invention provides a novel polypeptide, Connective Tissue Growth Factor (CTGF), polynucleotides encoding CTGF and polynucleotides regulating CTGF expression. The invention also provides agents that modulate CTGF and therapeutic methods for using the agents. Also provided are diagnostic methods for using CTGF and assays for identifying agents which affect the expression of CTGF polynucleotide

Methods of diagnosing a pathology characterized by a cell proliferative disorder associated with connective tissue growth factor

The present invention provides a novel polypeptide, Connective Tissue Growth Factor (CTGF), polynucleotides encoding CTGF, and including 5\u27 and 3\u27 untranslated nucleotides, antibodies reactive with CTGF and means for producing CTGF. Also provided are diagnostic and therapeutic methods for using CTGF, as well as an assay for identifying compositions which affect the expression of CTGF polynucleotide. The invention provides a novel TGF-.beta. responsive element upstream of the polynucleotide encoding CTGF structural gene