Transforming growth factor-beta1-induced hypertrophy and matrix expression in human bladder smooth muscle cells.
OBJECTIVE
To determine whether transforming growth factor beta (TGF-beta) could activate hyperplasia, hypertrophy, and altered collagen expression in human detrusor smooth muscle cells (SMCs).


METHODS
Human bladder SMCs were treated in vitro with TGF-beta1 and analyzed for changes in both proliferative and hypertrophic responses by cell number and volume measurements, as well as for alterations in extracellular matrix gene and protein expression by Northern blot and enzyme-linked immunosorbent assay.


RESULTS
Proliferation of bladder SMCs was refractory to TGF-beta1, whereas the cells became hypertrophic upon TGF-beta1 treatment. The interstitial collagens, types I and III, were increased significantly in TGF-beta1-treated cultures in a dose-dependent manner. These increases were blocked in the presence of TGF-beta1 neutralizing antibody and also when cultures were treated with the protein synthesis inhibitor cycloheximide, indicating that new protein synthesis is necessary for upregulation of the interstitial collagens. Messenger ribonucleic acid transcripts for both the COL1A1 and COL3A1 genes were elevated at 4, 6, and 24 hours in TGF-beta1-treated cultures, preceding the expression of the collagenous protein, showing that TGF-beta1 effects on bladder smooth muscle occur, at least in part, at the transcriptional level.


CONCLUSIONS
These results indicate that human bladder SMCs have the potential to mediate both a hypertrophic and fibrotic response upon TGF-beta1 stimulation.
Howard
Pamela S
PS
Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6030, USA. howard@biochem.dental.upenn.edu
Kucich
Umberto
U
Coplen
Douglas E
DE
He
Yuling
Y
D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen