Related Experiment Videos
Transforming growth factor-beta inhibits phosphate transport in renal epithelial cells
F Law1, R Rizzoli, J P Bonjour
1Department of Medicine, University Hospital, Geneva, Switzerland.
Abstract:
The effect(s) of transforming growth factor-beta (TGF-beta) on Pi transport was investigated in confluent opossum kidney (OK) epithelial cells. TGF-beta induced a time- and concentration-dependent decrease in the initial rate of sodium-dependent Pi, but not alanine, transport. This selective inhibitory effect on Pi transport was largely reversible and was not associated with a rise in adenosine 3',5'-cyclic monophosphate production. The reduction in Pi uptake was also independent of changes in extracellular calcium concentrations and prostaglandin synthesis. TGF-beta-mediated Pi transport inhibition appeared to involve neither pertussis toxin-sensitive G protein(s) nor augmented protein kinase C activity. However, the probable role of a serine/threonine protein kinase in signal transduction was supported by the considerable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta-induced Pi transport reduction was blunted by cycloheximide and abolished by actinomycin D. In conclusion, TGF-beta selectively inhibits the activity of the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. This action appears to be exerted via an unprecedented inhibitory pathway that might involve a serine/threonine protein kinase and alterations in the transcriptional and translational processes.
Insights
Transforming growth factor-beta (TGF-beta) selectively inhibits phosphate (Pi) transport in kidney cells. This effect involves a novel pathway impacting protein synthesis and kinase activity.
Area of Science:
- Cell Biology
- Renal Physiology
- Molecular Signaling
Background:
- Phosphate (Pi) transport is crucial for renal function.
- Transforming growth factor-beta (TGF-beta) is implicated in various cellular processes.
- The specific impact of TGF-beta on renal Pi transport remains incompletely understood.
Purpose of the Study:
- To investigate the effects of TGF-beta on sodium-dependent Pi transport in opossum kidney (OK) epithelial cells.
- To elucidate the molecular mechanisms underlying TGF-beta-mediated inhibition of Pi transport.
Main Methods:
- Utilized confluent opossum kidney (OK) epithelial cells.
- Measured initial rates of sodium-dependent Pi and alanine transport.
- Assessed effects of TGF-beta on adenosine 3',5'-cyclic monophosphate, extracellular calcium, prostaglandin synthesis, and protein kinase activity.
- Investigated involvement of G proteins, protein kinase C, serine/threonine protein kinase (using H-7), and gene expression (using cycloheximide and actinomycin D).
Main Results:
- TGF-beta induced a time- and concentration-dependent decrease in sodium-dependent Pi transport, but not alanine transport.
- The inhibition was reversible and not linked to changes in cAMP, calcium, or prostaglandins.
- The effect was independent of pertussis toxin-sensitive G proteins and augmented protein kinase C.
- TGF-beta's action was attenuated by H-7, suggesting a role for serine/threonine protein kinase.
- Inhibition was blunted by cycloheximide and abolished by actinomycin D, indicating involvement of transcriptional and translational processes.
Conclusions:
- TGF-beta selectively inhibits the sodium-dependent Pi transport system in the apical membrane of renal epithelial cells.
- This inhibition occurs through a novel pathway involving a serine/threonine protein kinase.
- The process likely involves alterations in transcriptional and translational mechanisms.