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Expression and clinical implications of PARs in the stenotic tissue of ureteropelvic junction obstruction
Tianyi Wang1, Mingcui Fu1, Xiangming Yan1
1Department of Urology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
Insights
Protease-activated receptors (PARs) are altered in pediatric ureteropelvic junction obstruction (UPJO). Decreased PAR2 expression in UPJO may disrupt UPJ peristalsis, while lower PAR1 suggests higher obstruction grade.
Area of Science:
- Urology
- Molecular Biology
- Pediatric Surgery
Background:
- Ureteropelvic junction obstruction (UPJO) is a common congenital anomaly.
- Protease-activated receptors (PARs) are implicated in various physiological processes.
- The role of PARs in UPJO pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the expression patterns of PARs in pediatric UPJO.
- To determine the clinical implications of PAR expression in UPJO.
- To elucidate the potential role of PARs in UPJO pathophysiology.
Main Methods:
- Immunohistochemistry to assess PAR distribution in normal and UPJO ureteropelvic junction (UPJ) tissues.
- Real-time quantitative PCR (RT-PCR) to measure PAR gene expression levels.
- Stratification of UPJO patients based on the Onen grading system.
Main Results:
- Immunofluorescence revealed reduced PAR2 expression in UPJO compared to controls.
- RT-PCR showed significantly lower mRNA expression of PAR2 in UPJO.
- PAR1 mRNA expression was notably lower in higher Onen grades (Onen-4) of UPJO.
Conclusions:
- PARs are present in the UPJ and interact with smooth muscle cells and interstitial cells.
- Decreased PAR1 expression correlates with increased UPJO severity (higher Onen grade).
- Downregulation of PAR2 may contribute to impaired neuromuscular transmission and peristalsis in UPJO.
Objective:
To explore the expression and clinical implications of protease activated receptors (PARs) in the pathogenesis of children with ureteropelvic junction obstruction (UPJO).
Material And Methods:
Immunohistochemistry was employed to investigate the distribution of PARs in both normal human ureteropelvic junction (UPJ) and cases of UPJO. Furthermore, PAR gene expression levels were assessed using real-time PCR (RT-PCR), and the patients in the UPJO group were stratified according to the Onen grading system. Subsequently, the clinical implications of PARs in UPJO were explored through RT-PCR analysis.
Results:
Immunofluorescence showed robust PAR2 expression in the control group compared with the UPJO group. The results of RT-PCR analysis revealed a significant decrease in the relative mRNA expression of PAR2 in the UPJO group compared to the control group. Notably, the relative RNA expression of PAR1 was significantly lower in the Onen-4 group compared to the control group. Furthermore, the relative mRNA expression of PAR2 exhibited a statistically significant difference among the Onen-3 group, Onen-4 group, and control group.
Conclusions:
PARs are widely distributed throughout the SIP syncytium of the UPJ and play a role in maintaining smooth muscle cells (SMCs) membrane potential by interacting with interstitial cells of Cajal (ICCs), as well as platelet-derived growth factor receptor alpha-positive cells (PDGFR α+ cells). The decreased expression of PAR1 suggests a higher preoperative Onen grade in UPJO patients. Furthermore, the downregulation of PAR2 effects at the UPJ may be involved in the loss of inhibitory neuromuscular transmission, disrupting the rhythmic peristalsis of the UPJ.
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