Collagen prolyl 4-hydroxylase is up-regulated in an acute bladder outlet obstruction

Lee, Sang Don; Akbal, Cem; Miseeri, Rosalia; Jung, Chaeyong; Rink, Richard; Kaefer, Martin

doi:10.1016/j.jpurol.2006.03.011

« Previous Next »Journal of Pediatric Urology
Volume 2, Issue 4 , Pages 225-232, August 2006

Collagen prolyl 4-hydroxylase is up-regulated in an acute bladder outlet obstruction

Sang Don Lee
- College of Medicine, Pusan National University, Busan, South Korea
Cem Akbal
- Department of Urology, Riley Hospital for Children, Indiana University, 702 Barnhill Drive, Indianapolis, IN 46202, USA
Rosalia Miseeri
- Department of Urology, Riley Hospital for Children, Indiana University, 702 Barnhill Drive, Indianapolis, IN 46202, USA
Chaeyong Jung
- Department of Urology, Riley Hospital for Children, Indiana University, 702 Barnhill Drive, Indianapolis, IN 46202, USA
Richard Rink
- Department of Urology, Riley Hospital for Children, Indiana University, 702 Barnhill Drive, Indianapolis, IN 46202, USA
Martin Kaefer
- Department of Urology, Riley Hospital for Children, Indiana University, 702 Barnhill Drive, Indianapolis, IN 46202, USA
- Correspondence author. Tel.: +1 317 274 8896; fax: +1 317 274 7481.

Received 26 September 2005; accepted 21 March 2006. published online 07 July 2006.

Abstract

Objective

Compliance is primarily related to extracellular matrix deposition, and prolyl 4-hydroxylase (P4Hs) plays a critical role in the synthesis of the matrix. To study the alteration of P4Hs, under the influence of variable hydrostatic pressure, a novel pressure device was used to expose human bladder smooth muscle cells (HBSMC) and fibroblasts (HBF) to pressures in the physiologic range. We then studied acute obstructed porcine bladder tissues to see if changes can also be seen after in-vitro obstruction.

Materials and methods

HBSMC and HBF were exposed to pressures at 0, 20 and 40cmH₂O for up to 72h. In-vivo studies were carried out next, using six normal (control) and five obstructed porcine bladders. Pigs were exposed to a consistent hydrostatic pressure of ≤20cm for 24h after ligation of the urethra. We used 2-DE to compare protein profiling of HBSMC under normal and increased pressures. Other analyses were used to detect molecular alteration and altered expression of mRNA for P4Hs.

Results

We identified 437 proteins from 476 spots (91.8%) obtained from HBSMC that were differentially expressed under normal and increased pressures. Under increased pressure, 48 unique proteins were significantly increased or decreased, and a prominent protein regulating extracellular matrix synthesis highly correlated with P4Hs. The exposure of both HBSMC and HBF to a sustained hydrostatic pressure resulted in the increased expression of P4Hs in a time- and pressure-dependent manner. In vivo, P4Hs expression was also significantly increased in the obstructed group.

Conclusions

P4Hs is up-regulated, in the human bladder, time and pressure dependently. The alteration of P4Hs over a short period may significantly influence the synthesis of extracellular matrix in vivo and lead to decreased compliance. Our results also support the concept that bladder outlet obstruction, with resultant pressures of 40cmH₂O or less, results in molecular changes consistent with decreased compliance.

Keywords: Prolyl 4-hydroxylase, Bladder smooth muscle, Bladder outlet obstruction