Glucose-mediated transforming growth factor-beta1 release in human mesothelial cells is endothelin independent.
Glucose and mechanical forces have been shown to be potent stimuli for mesothelial endothelin-1 release promoting profibrotic processes during peritoneal dialysis. We studied the osmolarity-induced and physical stress-induced effects on transforming growth factor-beta1 (TGF-beta1) release in human peritoneal mesothelial cells (HPMC), and analyzed whether a combined endothelin-A/endothelin-B receptor antagonist is able to mitigate HPMC TGF-beta1 release. D-Glucose and glycerol were used to analyze the impact of osmolarity on HPMC TGF-beta1 release. A cellular model of non-laminar fluid shear stress and cellular stretch was used to analyze the effects of physical forces. To neutralize the endothelin effects, a combined endothelin-A/endothelin-B receptor antagonist (LU 302 872) was chosen. Glucose, but not glycerol, increased mesothelial TGF-beta1 release in a concentration-dependent and time-dependent manner (P < 0.05 versus controls). Mechanical forces alone had no effect on mesothelial TGF-beta release. Combining fluid shear stress with high glucose medium led to a 30% increase (P = 0.019), and cellular stretch to a 34% increase (P = 0.075) in TGF-beta release compared with glucose stress alone. The combined endothelin-A/endothelin-B receptor antagonist had no impact on the mesothelial TGF-beta release. In conclusion, HPMC TGF-beta1 release by glucose and mechanical stress seems not to be related to the activity of the peritoneal endothelin system - at least in our in vitro model.
Morgera
Stanislao
S
Department of Nephrology, Charité, Humboldt University of Berlin, Germany.
Schlenstedt
Juliane
J
Giessing
Markus
M
Deger
Serdar
S
Hocher
Berthold
B
Neumayer
Hans-Hellmut
HH
D002478:Cells, Cultured; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D009852:Omentum / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D011422:Propionates / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; C113044:LU 224332; D011422:Propionates; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D053773:Transforming Growth Factor beta1; D005947:Glucose; D005990:Glycerol