Expression of pancreatitis associated proteins in urothelium and urinary afferent neurons following cyclophosphamide induced cystitis.

Abstract

We examined the expression profile of the members of the pancreatitis associated proteins/regenerating gene family in the bladder and in the primary afferent neurons of dorsal root ganglia using an animal model of cystitis. We examined the expression of pancreatitis-associated protein-I and pancreatitis-associated protein-III in the bladder and the dorsal root ganglia of female rats 4 hours, 48 hours or 10 days after cyclophosphamide (Sigma) injection using immunohistochemistry and reverse transcriptase-polymerase chain reaction. No pancreatitis-associated protein-III immunoreactivity was identified in control bladders but prominent expression was observed in the urothelium of animals with chronic cystitis. Cells expressing pancreatitis-associated protein-I were seen in the dorsal root ganglia but not in the bladder. In normal dorsal root ganglia pancreatitis-associated protein-I was expressed in a minor population of small diameter neurons (2.4%) that were also positive for isolectin-B4. However, by 10 days following the onset of cystitis the number of pancreatitis-associated protein-I positive neurons was increased (7.6%) and pancreatitis-associated protein-I immunoreactivity was further observed in a slightly larger group of neurons and tyrosine kinase A positive small neurons. The current results suggest that pancreatitis-associated protein-III is associated with bladder inflammation and they implicate pancreatitis-associated protein-I in the abnormal sensation in cystitis.