Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells.
Type beta transforming growth factor (TGF-beta) was shown to be the serum factor responsible for inducing normal human bronchial epithelial (NHBE) cells to undergo squamous differentiation. NHBE cells were shown to have high-affinity receptors for TGF-beta. TGF-beta induced the following markers of terminal squamous differentiation in NHBE cells: (i) increase in Ca ionophore-induced formation of crosslinked envelopes; (ii) increase in extracellular activity of plasminogen activator; (iii) irreversible inhibition of DNA synthesis; (iv) decrease in clonal growth rate; and (v) increase in cell surface area. The IgG fraction of anti-TGF-beta antiserum prevented both the inhibition of DNA synthesis and the induction of differentiation by either TGF-beta or whole blood-derived serum. Therefore, TGF-beta is the primary differentiation-inducing factor in serum for NHBE cells. In contrast, TGF-beta did not inhibit DNA synthesis of human lung carcinoma cells even though the cells possess comparable numbers of TGF-beta receptors with similar affinities for the factor. Epinephrine antagonized the TGF-beta-induced inhibition of DNA synthesis and squamous differentiation of NHBE cells. Although epinephrine increased the cyclic AMP levels in NHBE cells, TGF-beta did not alter the intracellular level in NHBE cells in either the presence or absence of epinephrine. Therefore, epinephrine and TGF-beta appear to affect different intracellular pathways that control growth and differentiation processes of NHBE cells.
Masui
T
T
Wakefield
L M
LM
Lechner
J F
JF
LaVeck
M A
MA
Sporn
M B
MB
Harris
C C
CC
D001980:Bronchi / Q000166:cytology* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D004847:Epithelial Cells; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D010455:Peptides / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors
D006133:Growth Substances; D010455:Peptides; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors; D000242:Cyclic AMP; D004837:Epinephrine