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Tumor Necrosis Factors: A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.Fibroblast Growth Factor 2: A single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. Several different forms of the human protein exist ranging from 18-24 kDa in size due to the use of alternative start sites within the fgf-2 gene. It has a 55 percent amino acid residue identity to FIBROBLAST GROWTH FACTOR 1 and has potent heparin-binding activity. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages. It was originally named basic fibroblast growth factor based upon its chemical properties and to distinguish it from acidic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 1).Transforming Growth Factors: Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA.Fibroblast Growth Factors: A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.Fibroblast Growth Factor 1: A 17-kDa single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. It binds to HEPARIN, which potentiates its biological activity and protects it from proteolysis. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages, and also has chemotactic and mitogenic activities. It was originally named acidic fibroblast growth factor based upon its chemical properties and to distinguish it from basic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 2).Receptors, Fibroblast Growth Factor: Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity.Receptor, IGF Type 1: A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The beta subunit contains an intrinsic tyrosine kinase domain.Receptor, Fibroblast Growth Factor, Type 1: A fibroblast growth factor receptor with specificity for FIBROBLAST GROWTH FACTORS; HEPARAN SULFATE PROTEOGLYCAN; and NEURONAL CELL ADHESION MOLECULES. Several variants of the receptor exist due to multiple ALTERNATIVE SPLICING of its mRNA. Fibroblast growth factor receptor 1 is a tyrosine kinase that transmits signals through the MAP KINASE SIGNALING SYSTEM.Receptor, Fibroblast Growth Factor, Type 2: A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in craniosynostotic syndromes (e.g., APERT SYNDROME; and CROUZON SYNDROME).Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Receptor, Fibroblast Growth Factor, Type 3: A fibroblast growth factor receptor that regulates CHONDROCYTE growth and CELL DIFFERENTIATION. Mutations in the gene for fibroblast growth factor receptor 3 have been associated with ACHONDROPLASIA; THANATOPHORIC DYSPLASIA and NEOPLASTIC CELL TRANSFORMATION.Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.Fibroblast Growth Factor 10: A fibroblast growth factor that is a mitogen for KERATINOCYTES. It activates FIBROBLAST GROWTH FACTOR RECEPTOR 2B and is involved in LUNG and limb development.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Receptor, Fibroblast Growth Factor, Type 4: A fibroblast growth factor receptor that is mainly expressed in LUNG; KIDNEY; PANCREAS; and SPLEEN. It also plays an important role in SKELETAL MUSCLE development and can contribute to NEOPLASTIC CELL TRANSFORMATION.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Insulin-Like Growth Factor II: A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults.Fibroblast Growth Factor 9: A fibroblast growth factor that was originally identified as a mitogen for GLIAL CELLS. It is expressed primarily in NEURONS.Fibroblast Growth Factor 4: A HEPARIN binding fibroblast growth factor that may play a role in LIMB BUDS development.Fibroblast Growth Factor 7: A fibroblast growth factor that is a specific mitogen for EPITHELIAL CELLS. It binds a complex of HEPARAN SULFATE and FIBROBLAST GROWTH FACTOR RECEPTOR 2B.Receptors, Somatomedin: Cell surface receptors that bind somatomedins and trigger intracellular changes which influence the behavior of cells. Studies have disclosed two types of receptors for this family of peptide hormones. The type I receptor is homologous to the insulin receptor and has tyrosine kinase activity. The type II receptor is identical to the mannose-6-phosphate receptor which is important in trafficking of lysosomal enzymes.Vascular Endothelial Growth Factor A: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.Receptors, Corticotropin-Releasing Hormone: Cell surface proteins that bind corticotropin-releasing hormone with high affinity and trigger intracellular changes which influence the behavior of cells. The corticotropin releasing-hormone receptors on anterior pituitary cells mediate the stimulation of corticotropin release by hypothalamic corticotropin releasing factor. The physiological consequence of activating corticotropin-releasing hormone receptors on central neurons is not well understood.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Fibroblast Growth Factor 8: A fibroblast growth factor that preferentially activates FIBROBLAST GROWTH FACTOR RECEPTOR 4. It was initially identified as an androgen-induced growth factor and plays a role in regulating growth of human BREAST NEOPLASMS and PROSTATIC NEOPLASMS.Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.Fibroblast Growth Factor 5: A fibroblast growth factor that may play a role in regulation of HAIR FOLLICLE phenotype. Spontaneous mutation of the gene for this protein results in a strain of MICE with abnormally long hair, referred to as angora mice.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.Endothelial Growth Factors: These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic FIBROBLAST GROWTH FACTORS but have different amino acid sequences.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Vascular Endothelial Growth Factors: A family of angiogenic proteins that are closely-related to VASCULAR ENDOTHELIAL GROWTH FACTOR A. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells.Kinetics: The rate dynamics in chemical or physical systems.Fibroblast Growth Factor 3: A fibroblast growth factor that is expressed primarily during development.Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.Nerve Growth Factors: Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.Cytotoxins: Substances that are toxic to cells; they may be involved in immunity or may be contained in venoms. These are distinguished from CYTOSTATIC AGENTS in degree of effect. Some of them are used as CYTOTOXIC ANTIBIOTICS. The mechanism of action of many of these are as ALKYLATING AGENTS or MITOSIS MODULATORS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Fibroblast Growth Factor 6: A fibroblast growth factor that was initially identified based on its sequence similarity to FIBROBLAST GROWTH FACTOR 4. It is found in MYOBLASTS and plays an important role in MUSCLE DEVELOPMENT.Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.Transforming Growth Factor alpha: An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.Heparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Receptors, Growth Factor: Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Urocortins: Neuropeptides of about 40 amino acids which are structurally similar to CORTICOTROPIN-RELEASING FACTOR. Unlike CRF acting primarily through type 1 CRF RECEPTORS, urocortins signal preferentially through type 2 CRF receptors. Urocortins have wide tissue distribution from fish to mammals, and diverse functions. In mammals, urocortins can suppress food intake, delays gastric emptying, and decreases heat-induced edema.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Receptor, Fibroblast Growth Factor, Type 5: The most divergent of the known fibroblast growth factor receptors. It does not contain an intracellular TYROSINE KINASE domain and has been shown to interact with FIBROBLAST GROWTH FACTOR 2. Fibroblast growth factor receptor 5 is found primarily in skeletal tissue.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Transforming Growth Factor beta1: A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Nerve Growth Factor: NERVE GROWTH FACTOR is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity.Time Factors: Elements of limited time intervals, contributing to particular results or situations.