Partial urethral obstruction: ATF3 and p-c-Jun are involved in the growth of the detrusor muscle and its motor innervation

Abstract

Objective. Infravesical obstruction leads to growth of urinary bladder smooth-muscle cells. The ganglion cells innervating the bladder muscle also increase in size. Stretch of detrusor muscle cells rapidly activates c-Jun NH₂-terminal kinase (JNK), which phosphorylates the transcription factor c-Jun, and stimulates the synthesis of the cotranscription factor ATF3. The aim of the study was to determine whether ATF3 and p-c-Jun were involved in growth of bladder smooth-muscle and ganglion cells. Material and methods. The urethra was partially obstructed in female rats. After 3 days or 10 weeks bladders were weighed, fixated and cut for immunohistochemistry to demonstrate ATF3 and p-c-Jun. Ganglia were processed separately. Unoperated and sham-operated rats were used as controls. Results. There was no ATF3 or p-c-Jun in control detrusor muscle. After 3 days of obstruction bladder weight had nearly doubled. Almost all nuclei in the detrusor showed immunofluorescence for ATF3 and p-c-Jun. After 10 weeks bladder weight had increased 10-fold. Almost all detrusor nuclei still showed p-c-Jun, but few had ATF3 activity. In control ganglia there was no ATF3 and only faint nuclear p-c-Jun activity. After 3 days of obstruction the ganglion cells had increased in size and many nuclei showed intense immunofluorescence for ATF3 and p-c-Jun. After 10 weeks the ganglion cell size had increased further. There was no ATF3 activity and no more p-c-Jun than in control ganglia. Conclusion. ATF3 and p-c-Jun seem to be involved in the growth of the detrusor muscle and its motor innervation following infravesical outlet obstruction.

Key Words::

• ATF3
• detrusor
• ganglia
• growth
• obstruction
• p-c-Jun
• urinary bladder

Acknowledgements

The present study was supported by grants from the Crafoord Foundation, governmental funding of clinical research within the National Health Service, and the Swedish Research Council.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.