Biomaterial Database

Mitogenic signals for thrombin in mesangial cells: regulation of phospholipase C and PDGF genes. 1989

P J Shultz, and T C Knauss, and P Mené, and H E Abboud

Department of Medicine, Veterans Administration Medical Center, Cleveland, Ohio.

Thrombin is a proteolytic enzyme of diverse biological activities, which is produced during activation of the coagulation pathway. In addition, thrombin is a mitogen for fibroblasts and endothelial cells. Intraglomerular thrombosis and cell proliferation are common pathological features of several glomerular diseases. We studied the effect of thrombin on deoxyribonucleic acid (DNA) synthesis in cultured human mesangial cells and explored mechanisms of signal transduction involved. Bovine and human thrombin caused dose-dependent increases in DNA synthesis, inositol trisphosphate, and cytosolic calcium [(Ca2+)i]. A threefold increase in inositol-3-trisphosphate (IP3) levels was observed as early as 10 s after the addition of thrombin, whereas increases in (Ca2+)i occurred within 5-10 s and declined rapidly. Stimulation of mesangial cells by thrombin resulted in induction of messenger ribonucleic acids (mRNAs) encoding platelet-derived growth factor (PDGF) A- and B-chains. This was associated with an enhanced secretion of PDGF-like protein. These data provide mechanisms by which thrombin may regulate mesangial cell function in disease states.

UI	MeSH Term	Description	Entries
D008934	Mitogens	Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)	Mitogen,Phytomitogen,Phytomitogens
D010716	Phosphatidylinositols	Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.	Inositide Phospholipid,Inositol Phosphoglyceride,Inositol Phosphoglycerides,Inositol Phospholipid,Phosphoinositide,Phosphoinositides,PtdIns,Inositide Phospholipids,Inositol Phospholipids,Phosphatidyl Inositol,Phosphatidylinositol,Inositol, Phosphatidyl,Phosphoglyceride, Inositol,Phosphoglycerides, Inositol,Phospholipid, Inositide,Phospholipid, Inositol,Phospholipids, Inositide,Phospholipids, Inositol
D010738	Type C Phospholipases	A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.	Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D010982	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.	Platelet Derived Growth Factor,Factor, Platelet-Derived Growth,Growth Factor, Platelet-Derived
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003600	Cytosol	Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.	Cytosols
D005786	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.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005920	Glomerular Mesangium	The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX.	Mesangium, Glomerular,Mesangial Extracellular Matrix,Extracellular Matrices, Mesangial,Extracellular Matrix, Mesangial,Glomerular Mesangiums,Matrices, Mesangial Extracellular,Matrix, Mesangial Extracellular,Mesangial Extracellular Matrices,Mesangiums, Glomerular
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man