Tumor protein P63 Regulated 1 contributes to inflammation and cell proliferation of cystitis glandularis through regulating the NF-кB/cyclooxygenase-2/prostaglandin E2 axis.

Songzhe Piao,Liangxue Sun,Yiran Tao,Mang Ke,Tao Hong

doi:10.17305/bjbms.2021.6763

Abstract

Cystitis glandularis is characterized by chronic inflammation and hyperproliferation of the bladder mucosa, and it contributes to the progression of bladder adenocarcinoma. Tumor Protein P63 Regulated 1 (TPRG1) is related to cellular inflammatory response, and dysregulation of TPRG1 in tumor tissues is associated with tumor recurrence. The effect of TPRG1 on cystitis glandularis was investigated in this study. Firstly, bladder specimens were isolated from patients with cystitis glandularis and Escherichia coli-induced cystitis rat. Expression of TPRG1 was found to be up-regulated in the bladder specimen. Moreover, adeno-associated virus (AAV)-mediated silencing of TPRG1 was injected into rat, and data from hematoxylin and eosin (H & E) staining showed that injection with AAV-shTPRG1 ameliorated E. coli-induced histological changes in bladder tissues of rats and suppressed the inflammatory response. Secondly, TPRG1 was also increased in primary cystitis glandularis cells. Knockdown of TPRG1 decreased cell proliferation and suppressed the migration of primary cystitis glandularis cells. Thirdly, cyclooxygenase-2 (COX-2) was up-regulated in the bladder specimens isolated from patients with cystitis glandularis and E. coli-induced cystitis rat. Injection with AAV-shTPRG1 reduced protein expression of COX-2, p65 and prostaglandin E2 (PGE2) in the bladder specimen. Finally, interference of COX-2 attenuated TPRG1 over-expression-induced increase in cell proliferation and migration in the primary cystitis glandularis cells. In conclusion, TPRG1 promoted inflammation and cell proliferation of cystitis glandularis through activation of NF-КB/COX2/PGE2 axis.

Highlights

Cystitis glandularis, a metaplastic mass of bladder mucosa, shows histopathologic appearance with submucosal urothelium and glandular metaplasia of the bladder mucosa [1]
The mRNA expression of Tumor Protein P63 Regulated 1 (TPRG1), cyclooxygenase (COX)1, COX2, mitogen-activated protein kinase (MAPK) 14, cyclin D1 (CCND1), histamine receptor H1 (HRH1), poly(ADP-ribose) polymerase 1 (PARP1), cyclin-dependent kinase 1 (CDK1) and Raf-1 ProtoOncogene, Serine/Threonine Kinase (RAF) was increased in the cystitis glandularis (CG) group compared with normal bladder specimens obtained from patients undergoing transurethral bladder tumor resection (Normal group) (Figure 1A)
Our results showed that the expression levels of TNF-α, IL-6, and IL-1β were enhanced in E. coli-induced cystitis rat, and knockdown of TPRG1 suppressed the inflammatory response in E. coli-induced cystitis rat through down-regulation of TNF-α, IL-6, and IL-1β

Summary

INTRODUCTION

A metaplastic mass of bladder mucosa, shows histopathologic appearance with submucosal urothelium and glandular metaplasia of the bladder mucosa [1]. Microarray analysis showed that TPRG1 was up-regulated in bladder mucosa isolated from cystitis glandularis patients [10]. The effects of TPRG1 on cell proliferation and inflammation in cystitis glandularis have not been reported yet. Chronic inflammation is a major risk factor for cystitis glandularis [11] and NF-кB signaling. This is important for secretion of proinflammatory cytokines, was activated in Escherichia coli -induced rat model with cystitis glandularis [12]. Expression of TPRG1 in bladder specimens isolated from patients with cystitis glandularis was determined first. The present study might provide a novel therapeutic target for cystitis glandularis

MATERIALS AND METHODS

RESULTS

DISCUSSION

CONCLUSION