Department of Urology, Taizhou Hospital of Zhejiang Province, Shaoxing University, Linhai, Zhejiang, China.
Department of Urology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
Bosn J Basic Med Sci. 2022 Feb 1;22(1):100-109. doi: 10.17305/bjbms.2021.6763.
Cystitis glandularis is characterized by chronic inflammation and hyperproliferation of bladder mucosa, and contributes to progression of bladder adenocarcinoma. TPRG1 (Tumor Protein P63 Regulated 1) is related to cellular inflammatory response, and dysregulation of TPRG1 in tumor tissues is associated with tumor early recurrence. The effect of TPRG1 on cystitis glandularis was investigated in this study. Firstly, bladder specimen were isolated from patients with cystitis glandularis and E. coli-induced cystitis rat. Expression of TPRG1 was found to be up-regulated in the bladder specimen. Moreover, adeno-associated virus (AAV)-mediated silence of TPRG1 was delivered into rat, and data from hematoxylin and eosin (H and 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 of primary cystitis glandularis cells, and suppressed the migration. Thirdly, cyclooxygenase-2 (COX-2) was up-regulated in the bladder specimen 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. Lastly, interference of COX-2 attenuated TPRG1 over-expression-induced increase of 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.
腺性膀胱炎的特征为慢性炎症和膀胱黏膜过度增生，并促进膀胱癌的进展。TPRG1（肿瘤蛋白 P63 调节因子 1）与细胞炎症反应有关，肿瘤组织中 TPRG1 的失调与肿瘤早期复发有关。本研究旨在探讨 TPRG1 对腺性膀胱炎的影响。首先，从腺性膀胱炎患者和大肠埃希菌诱导的膀胱炎大鼠的膀胱标本中分离出 TPRG1，发现其表达上调。此外，将腺相关病毒（AAV）介导的 TPRG1 沉默递送至大鼠体内，苏木精和伊红（H 和 E）染色数据显示，AAV-shTPRG1 注射可改善大鼠膀胱组织中大肠埃希菌诱导的组织学变化，并抑制炎症反应。其次，TPRG1 在原代腺性膀胱炎细胞中也增加。TPRG1 敲低可降低原代腺性膀胱炎细胞的增殖，并抑制迁移。第三，从腺性膀胱炎患者和大肠埃希菌诱导的膀胱炎大鼠的膀胱标本中发现环氧化酶-2（COX-2）上调。AAV-shTPRG1 注射可降低膀胱标本中 COX-2、p65 和前列腺素 E2（PGE2）的蛋白表达。最后，COX-2 的干扰可减弱 TPRG1 过表达诱导的原代腺性膀胱炎细胞增殖和迁移增加。总之，TPRG1 通过激活 NF-кB/COX2/PGE2 轴促进腺性膀胱炎的炎症和细胞增殖。
