Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA.
Purinergic Signal. 2022 Sep;18(3):267-287. doi: 10.1007/s11302-022-09875-1. Epub 2022 Jun 10.
P2 purinergic receptors are involved in the normal function of the kidney, bladder, and prostate via signaling that occurs in response to extracellular nucleotides. Dysregulation of these receptors is common in pathological states and often associated with disease initiation, progression, or aggressiveness. Indeed, P2 purinergic receptor expression is altered across multiple urologic disorders including chronic kidney disease, polycystic kidney disease, interstitial cystitis, urinary incontinence, overactive bladder syndrome, prostatitis, and benign prostatic hyperplasia. P2 purinergic receptors are likewise indirectly associated with these disorders via receptor-mediated inflammation and pain, a common characteristic across most urologic disorders. Furthermore, select P2 purinergic receptors are overexpressed in urologic cancer including renal cell carcinoma, urothelial carcinoma, and prostate adenocarcinoma, and pre-clinical studies depict P2 purinergic receptors as potential therapeutic targets. Herein, we highlight the compelling evidence for the exploration of P2 purinergic receptors as biomarkers and therapeutic targets in urologic cancers and other urologic disease. Likewise, there is currently optimism for P2 purinergic receptor-targeted therapeutics for the treatment of inflammation and pain associated with urologic diseases. Further exploration of the common pathways linking P2 purinergic receptor dysregulation to urologic disease might ultimately help in gaining new mechanistic insight into disease processes and therapeutic targeting.
P2 嘌呤能受体通过细胞外核苷酸反应信号参与肾脏、膀胱和前列腺的正常功能。这些受体的失调在病理状态下很常见，通常与疾病的起始、进展或侵袭性有关。事实上，P2 嘌呤能受体的表达在多种泌尿科疾病中发生改变，包括慢性肾脏病、多囊肾病、间质性膀胱炎、尿失禁、膀胱过度活动症、前列腺炎和良性前列腺增生。P2 嘌呤能受体也通过受体介导的炎症和疼痛与这些疾病间接相关，这是大多数泌尿科疾病的共同特征。此外，一些选择性 P2 嘌呤能受体在包括肾细胞癌、尿路上皮癌和前列腺腺癌在内的泌尿科癌症中过度表达，临床前研究表明 P2 嘌呤能受体是潜在的治疗靶点。在此，我们强调了探索 P2 嘌呤能受体作为泌尿科癌症和其他泌尿科疾病的生物标志物和治疗靶点的有力证据。同样，目前人们对针对 P2 嘌呤能受体的治疗药物治疗与泌尿科疾病相关的炎症和疼痛持乐观态度。进一步探索将 P2 嘌呤能受体失调与泌尿科疾病联系起来的共同途径，可能最终有助于深入了解疾病过程和治疗靶点。
