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Cytokine & Growth Factor Reviews Sep 1997Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that binds heparin and is secreted by fibroblasts after activation with transforming growth... (Review)
Review
Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that binds heparin and is secreted by fibroblasts after activation with transforming growth factor beta (TGF-beta). CTGF is a member of a highly conserved family of peptides that include immediate early gene products cef10, cyr61, fisp12; a putative avian proto-oncogene, nov; and a drosophila gene, twisted gastrulation, tsg, that controls medial mesoderm induction during dorsal-ventral axis pattern formation, a process also controlled by TGF-beta related peptides (dpp, scw). In the adult mammal, CTGF functions as a downstream mediator of TGF-beta action on connective tissue cells, where it stimulates cell proliferation and extracellular matrix synthesis. CTGF does not appear to act on epithelial cells or immune cells. Because the biological actions of TGF-beta are complex and affect many different cell types, CTGF may serve as a more specific target for selective intervention in processes involving connective tissue formation during wound repair or fibrotic disorders. Northern blot and in situ hybridization studies have demonstrated that CTGF is coordinately expressed with TGF-beta in every fibrotic disorder examined to date. Agents that inhibit CTGF production or action could lead to the development of new therapeutic approaches for the control of fibrotic disorders in humans.
Topics: Animals; Connective Tissue Growth Factor; Fibroblasts; Gene Expression Regulation; Growth Substances; Humans; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Mitogens; Nephroblastoma Overexpressed Protein; Proto-Oncogene Mas; Transforming Growth Factor beta
PubMed: 9462483
DOI: 10.1016/s1359-6101(97)00010-5 -
Immunology Apr 1978Various strains of the murine mycoplasma M. neurolyticum have been shown to induce extensive blast transformation of mouse lymphocytes, comparable in strength to...
Various strains of the murine mycoplasma M. neurolyticum have been shown to induce extensive blast transformation of mouse lymphocytes, comparable in strength to mitogenicity exerted by these mycoplasma species on rat lymphocytes. The data summarized in this report demonstrate that this mitogenic effect is non-specific. Lymphoid cells from mycoplasma free, germ-free mice were activated to the same extent as those lymphocytes obtained from conventionally bred animals. Lymph node cell suspensions obtained from athymic nude mice were strongly activated by M. neurolyticum mitogen. Furthermore, mouse thymocytes and mouse T-cell enriched populations, were not stimulated by these mitogens. It was thus suggested that M. neurolyticum activates mouse B lymphocytes.
Topics: Animals; B-Lymphocytes; Female; Germ-Free Life; Lymphocyte Activation; Male; Mice; Mice, Inbred ICR; Mice, Nude; Mitogens; Mycoplasma; T-Lymphocytes; Thymidine
PubMed: 309850
DOI: No ID Found -
International Journal of... 1986Nocardia water soluble mitogen (NWSM), which is a peptidoglycan, was prepared from Nocardia opaca. Its effect on human B-lymphocyte proliferation, the number of...
Nocardia water soluble mitogen (NWSM), which is a peptidoglycan, was prepared from Nocardia opaca. Its effect on human B-lymphocyte proliferation, the number of immunoglobulin secreting B-cells, and bone marrow stem cell growth was studied in vitro. NWSM stimulated the proliferation of B-lymphocytes of all ten healthy subjects studied very effectively (P less than 0.0005). No T-cell activation occurred. NWSM did not increase the amount of antibody producing cells. The growth of bone marrow stem cells was enhanced only in one patient out of the eight studied. Thus NWSM is a B-lymphocyte mitogen with a potential effect on hematopoietic stem cells. However, production of NWSM was faced with difficulties because not all lots prepared had B-cell stimulating activity.
Topics: Antibody-Producing Cells; B-Lymphocytes; Hematopoiesis; Humans; In Vitro Techniques; Lymphocyte Activation; Mitogens; Nocardia; Solubility; Water
PubMed: 3492453
DOI: 10.1016/0192-0561(86)90096-2 -
Acta Crystallographica. Section F,... Mar 2006Superantigens are bacterial or viral toxins with potent immunostimulatory properties. Streptococcus dysgalactiae-derived mitogen, a 25 kDa protein, is a recently...
Superantigens are bacterial or viral toxins with potent immunostimulatory properties. Streptococcus dysgalactiae-derived mitogen, a 25 kDa protein, is a recently discovered superantigen isolated from S. dysgalactiae culture supernatant. Sequence considerations suggest that it belongs to a new superantigen family distinct from other superantigens. The protein was expressed in Escherichia coli cells and purified to homogeneity. Crystals were grown at pH 4.2-4.4 in the presence of 18-20%(w/v) PEG 3350 and 0.4 M lithium nitrate. A complete data set to 2.4 A resolution was collected from a single crystal at liquid-nitrogen temperatures using synchrotron radiation. The crystals belong to space group P3/P3(1)/P3(2), with unit-cell parameters a = b = 52.7, c = 62.4 A, gamma = 120 degrees and one molecule in the crystallographic asymmetric unit.
Topics: Crystallization; Crystallography, X-Ray; Escherichia coli; Mitogens; Streptococcus; Superantigens
PubMed: 16511312
DOI: 10.1107/S1744309106003678 -
Planta Medica Mar 2005Kaurene-type diterpenes possess various biological activities including antitumor and anti-inflammatory effects. Indeed, we have found that an ent-kaurene diterpene,...
Kaurene-type diterpenes possess various biological activities including antitumor and anti-inflammatory effects. Indeed, we have found that an ent-kaurene diterpene, ent-11alpha-hydroxy-16-kauren-15-one (KD), induced apoptosis via caspase-8 activation in human promyelocytic leukemia HL-60 cells. However, the mechanism of caspase-8 activation by KD is not clear. In this study, we investigated the involvement of p38 mitogen-activated protein kinase (p38 (MAPK)) in KD-induced apoptosis. p38 (MAPK) was activated by treatment with KD parallel to DNA ladder formation. Pretreatment with SB203580, a specific inhibitor of p38 (MAPK), attenuated induction of apoptosis by KD and inhibited activation of caspase-8. Cleavage of Bid, a typical substrate of caspase-8, was also inhibited by treatment with SB203580, suggesting that activation of p38 (MAPK) occurs upstream of caspase-8 during KD-induced apoptosis.
Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Diterpenes, Kaurane; HL-60 Cells; Humans; Isodon; Mitogens; Phytotherapy; Plant Extracts; p38 Mitogen-Activated Protein Kinases
PubMed: 15770551
DOI: 10.1055/s-2005-837830 -
Microbiology and Immunology 1979A water-soluble mitogen was extracted with hot-water from the fruiting bodies of a fungus, Peziza vesiculosa, collected in the wild. The active substance, named...
A water-soluble mitogen was extracted with hot-water from the fruiting bodies of a fungus, Peziza vesiculosa, collected in the wild. The active substance, named vesiculogen, was able to stimulate selectively murine B cells because mitogenic activity was observed in the spleen cell cultures of congenitally athymic nude mice, but not in the thymus cell cultures. The possibility that the mitogenicity of vesiculogen was due to lipopolysaccharide was denied completely by the following evidence: 1) lipopolysaccharide in vesiculogen was undetectable(less than 0.001% in the Limulus test), 2) vesiculogen was able to stimulate strongly DNA synthesis of spleen cells from C3H/HeJ mice, and 3) the mitogenic activity of vesiculogen was not inhibited by polymyxin B. Vesiculogen increased antigen-nonspecifically the number of direct plaque forming cells to sheep erythrocytes, horse erythrocytes, and trinitrophenylated-horse erythrocytes. This result shows that vesiculogen acts as a polyclonal B cell activator on murine spleen cells.
Topics: Animals; Ascomycota; B-Lymphocytes; Concanavalin A; DNA; Dose-Response Relationship, Immunologic; Fungal Proteins; Kinetics; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Nude; Mitogens; Peptidoglycan; Spleen; T-Lymphocytes
PubMed: 316098
DOI: 10.1111/j.1348-0421.1979.tb00530.x -
The Journal of Neuroscience : the... Dec 1994To characterize mitogens that might contribute to Schwann cell proliferation during development or in tumors, we tested the ability of hepatocyte growth factor (HGF) to...
To characterize mitogens that might contribute to Schwann cell proliferation during development or in tumors, we tested the ability of hepatocyte growth factor (HGF) to stimulate Schwann cell division in vitro. HGF is a potent mitogen for purified rat Schwann cells; DNA synthesis in rat Schwann cells was stimulated 20-40-fold by 3-10 ng/ml HGF. Rat Schwann cells express c-met mRNA, encoding the HGF receptor, but not HGF mRNA, implying that HGF might act as a paracrine Schwann cell growth factor. HGF-stimulated Schwann cell proliferation differs from that of previously described Schwann cell mitogens in that its activity is abolished by forskolin and is not inhibited or potentiated by addition of transforming growth factor beta (TGF beta) or fibroblast growth factor (FGF). HGF is probably not a component of the axonal signal thought to cause Schwann cell division during development, as anti-HGF neutralizing antibodies failed to block neuron-stimulated Schwann cell proliferation. In contrast, mitogenic activity present in normal human adult nerves and in neurofibromas from patients with type 1 neurofibromatosis analyzed in the absence of forskolin is largely inhibitable by anti-HGF. Thus, HGF is a novel mitogen for Schwann cells in vitro and it is present in Schwann cell tumors, suggesting a potential role for HGF after wounding of peripheral nerves or in tumor growth.
Topics: Adolescent; Adult; Aged; Animals; Base Sequence; Child; Colforsin; Female; Ganglia, Spinal; Hepatocyte Growth Factor; Humans; Male; Middle Aged; Mitogens; Molecular Probes; Molecular Sequence Data; Neurofibroma; Proto-Oncogene Proteins c-met; RNA, Messenger; Rats; Receptor Protein-Tyrosine Kinases; Schwann Cells
PubMed: 7996175
DOI: 10.1523/JNEUROSCI.14-12-07284.1994 -
Metabolism: Clinical and Experimental Apr 1987Bone-derived proteins have been shown to stimulate the proliferation of bone-forming cells and to increase the rate of embryonic bone formation in vitro. The current...
Bone-derived proteins have been shown to stimulate the proliferation of bone-forming cells and to increase the rate of embryonic bone formation in vitro. The current studies were intended to determine the tissue distribution of bone cell-active mitogen(s) in the embryonic chick, to determine the cellular origin and the target cell specificity of the bone cell-active mitogen(s) in embryonic chick bone, to determine whether the release of mitogenic activity from embryonic chick tibiae was proportional to bone resorption, and to compare mitogenic activities prepared from different skeletal sources, with respect to Mr, chemical stability, and mitogen activity kinetics. A bone cell-active mitogen(s) was identified in extracts of bone and cartilage but not in extracts of muscle, liver, intestine, or brain. (Mitogenic activity was determined as increased incorporation of 3[H]-thymidine into DNA in serum-free, calvarial cell cultures.) Together, the following three observations indicate an osteoblastic origin for the bone cell-active mitogen(s) in chick bone. First, the mitogen content of embryonic chick tibiae increased 4.5-fold, during eight days of serum-free in vitro growth (P less than .005). Second, conditioned medium (CM) from serum-free monolayer cultures of calvarial cells contained bone cell-active mitogen(s), but CM from parallel cultures of skin, liver, and intestinal cells did not. And, finally, the amount of bone cell-active mitogen(s) in calvarial cell CM was correlated with the amount of alkaline phosphatase (ALP) activity per cell, ie, an index of osteoblastic differentiation (r = .92, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Bone Resorption; Bone and Bones; Chick Embryo; Cycloheximide; Insulin; Mitogens; Osteogenesis; Parathyroid Hormone
PubMed: 3550371
DOI: 10.1016/0026-0495(87)90200-9 -
The Journal of Investigative Dermatology Jul 2001Wound re-epithelialization represents a tissue movement that crucially participates in wound closure. Recently, we demonstrated that supplemented leptin improved...
Wound re-epithelialization represents a tissue movement that crucially participates in wound closure. Recently, we demonstrated that supplemented leptin improved re-epithelialization processes in leptin-deficient ob/ob mice. In this study we investigated regulation of the leptin system during normal repair in healthy animals. We found leptin to be present at the wound site during healing, although leptin levels were clearly reduced upon injury compared with uninvolved control skin. The functional leptin receptor subtype obRb was observed to be constitutively expressed in nonwounded skin. During early healing, the leptin receptor obRb was downregulated, but re-increased again from day 5 postwounding. Immunohistochemistry revealed that highly proliferative keratinocytes of the wound margin epithelia strongly expressed the functional leptin receptor subtype obRb. In vitro studies demonstrated that murine and human primary epidermal keratinocytes responded to exogenously added leptin with a proliferative response. Moreover, specificity of leptin-mediated mitogenic effects on primary keratinocytes could be shown by completely blocking leptin actions by a soluble, nonfunctional chimeric leptin receptor. Finally, we report that leptin, besides the recently described activation of the janus tyrosine kinase signal transducers, also activated extracellular signal-regulated kinase-controlled signaling pathways in primary keratinocytes.
Topics: Animals; Carrier Proteins; Cell Division; Down-Regulation; Epidermal Cells; Epidermis; Female; Gene Expression; Keratinocytes; Leptin; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Mitogens; RNA, Messenger; Receptors, Cell Surface; Receptors, Leptin; Wound Healing
PubMed: 11442755
DOI: 10.1046/j.0022-202x.2001.01387.x -
FEBS Letters Sep 1986Three agents which are mitogenic for T lymphocytes (phytohaemagglutinin, monoclonal antibody UCHT 1 and 12-O-tetradecanoylphorbol-13-acetate) stimulated rapid...
Three agents which are mitogenic for T lymphocytes (phytohaemagglutinin, monoclonal antibody UCHT 1 and 12-O-tetradecanoylphorbol-13-acetate) stimulated rapid phosphorylation of a 42 kDa protein in permeabilized T lymphocytes. Phosphorylation occurred on tyrosine and serine residues. A non-mitogenic monoclonal antibody (RFT11) did not stimulate phosphorylation of this protein. Furthermore, the dose response of 42 kDa protein phosphorylation and of mitogenesis to increasing amounts of phytohaemagglutinin were closely similar. We therefore propose that mitogen-stimulated phosphorylation of the 42 kDa protein is part of the mechanism for transduction of mitogenic signals in lymphocytes. To our knowledge, this is the first report of rapid, ligand-stimulated tyrosine protein phosphorylation in T lymphocytes.
Topics: Antibodies, Monoclonal; Cell Membrane Permeability; Humans; Mitogens; Phosphoproteins; Phosphorylation; Phytohemagglutinins; Serine; T-Lymphocytes; Tetradecanoylphorbol Acetate; Tyrosine
PubMed: 3093274
DOI: 10.1016/0014-5793(86)81339-4