Insulin-like growth factor axis in airway smooth muscle cells.
Insulin-like growth factors (IGFs) mediate cell proliferation and differentiation and bind with high affinities and specificities to IGF receptors and IGF-binding proteins (IGFBPs). We examined the roles of these three groups of proteins in cultured rabbit airway smooth muscle (ASM) cells. Affinity cross-linking of IGF-I and IGF-II to membranes of ASM cells revealed type 1 and type 2 IGF receptors. Western ligand blot analysis of ASM cell-conditioned medium revealed the presence of a single IGFBP band that precipitated with an antibody specific to IGFBP-2. ASM cells secreted radioimmunoassayable IGF-II; however, no IGF-I was detected under the same conditions. Two molecular weight forms of IGF-II were produced by the ASM cells. Exposure of cells to 1,000 ng/ml of IGF-I stimulated them to proliferate to 230 +/- 9.7% of their respective controls. Exposure to 1,000 ng/ml of IGF-II was approximately 40% as effective as exposure to 1,000 ng/ml of IGF-I. Both IGF-I and IGF-II exhibited binding to the type 1 IGF receptor. In summary, IGFs are mitogens for cultured rabbit ASM cells, and their actions are most likely mediated through the type 1 IGF receptor. The ASM cells secrete IGF-II and IGFBP-2, and the latter could modulate the actions of the IGFs in these cells.
Noveral
J P
JP
Department of Pediatrics, Joseph Stokes, Jr., Research Institute, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine 19104.
Bhala
A
A
Hintz
R L
RL
Grunstein
M M
MM
Cohen
P
P
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018969:Insulin-Like Growth Factor Binding Proteins; D009130:Muscle, Smooth / Q000378:metabolism*; D011817:Rabbits; D017451:Receptors, Somatomedin / Q000032:analysis; D013002:Somatomedins / Q000096:biosynthesis* / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D017451:Receptors, Somatomedin; D013002:Somatomedins