BIOMAT Database Logo BIOMAT Database Logo

Expression and insulin-like growth factor-dependent proteolysis of insulin-like growth factor-binding protein-4 are regulated by cell confluence in vascular smooth muscle cells. 1994

A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Division of Cardiology, Cedars-Sinai Medical Center, UCLA School of Medicine 90048.

Insulin-like growth factor (IGF)-I is markedly induced after balloon injury in the rat aorta, where it may serve to mediate vascular repair. Because the bioavailability of IGF-I is modulated by IGF-binding proteins (IGFBPs), we examined the regulation of IGFBPs by IGFs in primary cultures of rat aortic smooth muscle cells (SMCs). Serum-deprived SMC-conditioned medium contains IGFBPs of 38 to 45 kD (only in confluent cultures), 30 kD (possibly IGFBP-2), 28 kD, and 24 kD (IGFBP-4), the latter being the most abundant. IGF-I and IGF-II but not insulin evoked a marked decrease of IGFBP-4 as early as 4 hours after treatment. IGFBP-4 mRNA abundance, however, was entirely unaffected by IGF-I for up to 48 hours. IGF-I analogues with high affinity for the IGF-I receptor and weak affinity for IGFBP paradoxically evoked a small increase in IGFBP-4, probably through a general increase in protein synthesis. IGF-I only minimally decreased IGFBP-4 content in medium of sparse cultures, whereas it completely abolished IGFBP-4 content in conditioned medium of superconfluent SMCs. IGF-I also evoked a concentration-dependent increase in the abundance of IGFBP-3 in confluent, but not sparse, SMCs without affecting IGFBP-3 mRNA. Addition of IGF-I to cell-free medium conditioned by confluent, but not by sparsely cultured, SMCs led to rapid degradation of IGFBP-4. Interestingly, IGFBP-4 mRNA was markedly induced in confluent relative to sparsely grown SMCs in an IGF-I independent fashion. Thus, both biosynthesis and IGF-dependent proteolysis of IGFBP-4 are increased in confluent SMCs. Proteolysis was maximal at 37 degrees C and was abrogated by EDTA and by benzamidine. Phenylmethylsulfonyl fluoride and the plasmin inhibitor bdellin had minor inhibitory activity, whereas aprotinin, angiotensin-converting enzyme inhibitors, and N-ethylmaleimide were without effect. The protease does not affect the structure of IGF-I as determined by reverse-phase high-performance liquid chromatography and size-exclusion chromatography of 125I-IGF-I incubated for up to 24 hours with SMC-conditioned medium containing IGFBP-4. In summary, SMCs elaborate a cation-dependent protease in a confluence-dependent fashion, which degrades bound IGFBP-4 and likely releases free structurally intact IGF-I, presumably to interact with the cell surface receptor and/or other IGFBPs.

UI MeSH Term Description Entries
D007334 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. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008297 Male Males
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D010450 Endopeptidases A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS. Endopeptidase,Peptide Peptidohydrolases
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002478 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. Cultured Cells,Cell, Cultured,Cultured Cell
D004492 Edetic Acid A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive. EDTA,Edathamil,Edetates,Ethylenediaminetetraacetic Acid,Tetracemate,Calcium Disodium Edetate,Calcium Disodium Versenate,Calcium Tetacine,Chelaton 3,Chromium EDTA,Copper EDTA,Coprin,Dicobalt EDTA,Disodium Calcitetracemate,Disodium EDTA,Disodium Ethylene Dinitrilotetraacetate,Distannous EDTA,Edetate Disodium Calcium,Edetic Acid, Calcium Salt,Edetic Acid, Calcium, Sodium Salt,Edetic Acid, Chromium Salt,Edetic Acid, Dipotassium Salt,Edetic Acid, Disodium Salt,Edetic Acid, Disodium Salt, Dihydrate,Edetic Acid, Disodium, Magnesium Salt,Edetic Acid, Disodium, Monopotassium Salt,Edetic Acid, Magnesium Salt,Edetic Acid, Monopotassium Salt,Edetic Acid, Monosodium Salt,Edetic Acid, Potassium Salt,Edetic Acid, Sodium Salt,Ethylene Dinitrilotetraacetate,Ethylenedinitrilotetraacetic Acid,Gallium EDTA,Magnesium Disodium EDTA,N,N'-1,2-Ethanediylbis(N-(carboxymethyl)glycine),Potassium EDTA,Stannous EDTA,Versenate,Versene,Acid, Edetic,Acid, Ethylenediaminetetraacetic,Acid, Ethylenedinitrilotetraacetic,Calcitetracemate, Disodium,Dinitrilotetraacetate, Disodium Ethylene,Dinitrilotetraacetate, Ethylene,Disodium Versenate, Calcium,EDTA, Chromium,EDTA, Copper,EDTA, Dicobalt,EDTA, Disodium,EDTA, Distannous,EDTA, Gallium,EDTA, Magnesium Disodium,EDTA, Potassium,EDTA, Stannous,Edetate, Calcium Disodium,Ethylene Dinitrilotetraacetate, Disodium,Tetacine, Calcium,Versenate, Calcium Disodium
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
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

Related Publications

A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Insulin-like growth factor binding protein production by bovine and human vascular smooth muscle cells: production of insulin-like growth factor binding protein-6 by human smooth muscle.
December 1996, Endocrinology,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.
February 1994, The American journal of the medical sciences,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Differential expression and biological effects of insulin-like growth factor-binding protein-4 and -5 in vascular smooth muscle cells.
July 1998, The Journal of biological chemistry,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Vascular smooth muscle cells synthesize two forms of insulin-like growth factor binding proteins which are regulated differently by the insulin-like growth factors.
October 1993, Journal of cellular physiology,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Insulin-like growth factor binding protein-4 expression is decreased by angiotensin II and thrombin in rat aortic vascular smooth muscle cells.
February 2000, Arteriosclerosis, thrombosis, and vascular biology,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Tumor necrosis factor-alpha regulates insulin-like growth factor-1 and insulin-like growth factor binding protein-3 expression in vascular smooth muscle.
March 2002, Circulation,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Insulin-like growth factor binding proteins-2 to -6 are expressed by human vascular smooth muscle cells.
November 1999, The Journal of endocrinology,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Alterations in insulin-like growth factor (IGF)-dependent IGF-binding protein-4 proteolysis in transformed osteoblastic cells.
April 1995, Endocrinology,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Insulin-like growth factor binding protein proteolysis.
January 2003, Trends in endocrinology and metabolism: TEM,
A Kamyar, and C J Pirola, and H M Wang, and B Sharifi, and S Mohan, and J S Forrester, and J A Fagin
Properties of an insulin-like growth factor-binding protein-4 protease that is secreted by smooth muscle cells.
June 1995, Endocrinology,
Copied contents to your clipboard!