Biomaterial Database

Transforming growth factor-beta increases transcription of the genes encoding the epidermal growth factor receptor and fibronectin in normal rat kidney fibroblasts. 1988

K L Thompson, and R Assoian, and M R Rosner

Department of Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge 02139.

Transforming growth factor-beta (TGF-beta) is a potent modulator of cell growth in many systems. In normal rat kidney (NRK) fibroblasts, TGF-beta synergizes with epidermal growth factor (EGF) to stimulate growth in soft agar, a characteristic of the transformed phenotype. Many biochemical effects of TGF-beta occur at the cell surface. Increased binding of EGF and synthesis of extracellular matrix components such as fibronectin and collagen are primary responses of NRK cells to TGF-beta. Although specific membrane receptors for TGF-beta have been identified, the mechanism of action of this factor is not well understood. Here we demonstrate that TGF-beta enhances the expression of the EGF receptor in NRK cells through an increase in the level of EGF receptor gene transcripts. Analysis of nuclear run-off transcription levels and mRNA half-lives indicate that the elevation in EGF-receptor mRNA results from an increase in the rate of transcription. Dose-response and kinetic studies suggest that the EGF receptor response to TGF-beta is biphasic, possibly resulting from the action of multiple TGF-beta receptors. TGF-beta also elevates the levels of fibronectin and tubulin transcripts in NRK cells; however, the mechanism differs for each gene. The increase in fibronectin mRNA in response to TGF-beta results from an increased rate of gene transcription. Tubulin mRNA levels, in contrast, appear to be post-transcriptionally regulated. These results implicate TGF-beta as a transcriptional activator of the genes for both the EGF receptor and fibronectin and suggest the two genes may be regulated through a common pathway in this cell type.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
D005353	Fibronectins	Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.	Cold-Insoluble Globulins,LETS Proteins,Fibronectin,Opsonic Glycoprotein,Opsonic alpha(2)SB Glycoprotein,alpha 2-Surface Binding Glycoprotein,Cold Insoluble Globulins,Globulins, Cold-Insoluble,Glycoprotein, Opsonic,Proteins, LETS,alpha 2 Surface Binding Glycoprotein
D005796	Genes	A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.	Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012333	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.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014158	Transcription, Genetic	The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.	Genetic Transcription
D015291	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.	Transforming Growth Factor,Factor, Transforming Growth,Factors, Transforming Growth,Growth Factor, Transforming,Growth Factors, Transforming