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P2 purinergic receptor dysregulation in urologic disease
Janielle P Maynard1,2, Karen S Sfanos3,4,5
1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. maynard@jhmi.edu.
Abstract:
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.
Insights
P2 purinergic receptors play key roles in urologic health. Their dysregulation is linked to various urologic diseases and cancers, suggesting potential as therapeutic targets and biomarkers.
Area of Science:
- Urology
- Molecular Biology
- Pharmacology
Background:
- P2 purinergic receptors mediate cellular functions in the kidney, bladder, and prostate through extracellular nucleotide signaling.
- Dysregulation of P2 purinergic receptors is implicated in the initiation, progression, and aggressiveness of various urologic disorders.
- Altered P2 purinergic receptor expression is observed in chronic kidney disease, polycystic kidney disease, interstitial cystitis, urinary incontinence, overactive bladder syndrome, prostatitis, and benign prostatic hyperplasia.
Purpose of the Study:
- To review the compelling evidence for P2 purinergic receptors as biomarkers and therapeutic targets in urologic diseases.
- To highlight the role of P2 purinergic receptors in inflammation and pain associated with urologic conditions.
- To explore the potential of targeting P2 purinergic receptors for novel therapeutic strategies.
Main Methods:
- Literature review and analysis of existing pre-clinical and clinical studies.
- Examination of P2 purinergic receptor expression patterns in various urologic disorders and cancers.
- Assessment of the association between P2 purinergic receptors and disease-related inflammation and pain.
Main Results:
- P2 purinergic receptors are altered in numerous urologic diseases, including chronic kidney disease and benign prostatic hyperplasia.
- Overexpression of specific P2 purinergic receptors is noted in urologic cancers such as renal cell carcinoma and prostate adenocarcinoma.
- P2 purinergic receptors are indirectly linked to urologic disorders through receptor-mediated inflammation and pain.
Conclusions:
- P2 purinergic receptors represent promising biomarkers and therapeutic targets for urologic cancers and other urologic diseases.
- Targeted therapeutics for P2 purinergic receptors offer optimism for treating inflammation and pain in urologic conditions.
- Further research into the pathways linking P2 purinergic receptor dysregulation to urologic disease may yield new mechanistic insights and therapeutic approaches.
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