The following is a summary of “De-obstruction of bladder outlet in humans reverses organ remodeling by normalizing the expression of key transcription factors,” published in the February 2024 issue of Urology by Akshay et al.

Benign prostatic hyperplasia (BPH) frequently leads to bladder outlet obstruction, termed benign prostatic obstruction (BPO), manifesting as lower urinary tract symptoms and urodynamic alterations. Surgical intervention, such as transurethral resection of the prostate (TURP), is often required when conservative treatments fail. Understanding the molecular changes induced by BPO in the human bladder and their reversal post-de-obstruction is crucial for determining the point at which organ deterioration becomes irreversible. Here, the researchers conducted a comprehensive molecular and urodynamic analysis of bladders in men with BPO before TURP and three months after obstruction relief.

The study group performed integrated transcriptome and proteome analyses of bladder samples from male BPO patients before and after TURP surgery. mRNA and protein profiles were correlated with urodynamic findings, specifically voiding detrusor pressure (PdetQmax) before TURP. Molecular classifiers of each group were identified to delineate pre-TURP bladder status.

BPO patients without detrusor overactivity (DO) were categorized into high-pressure (HP) and medium-pressure (MP) groups based on PdetQmax values. Three months post-TURP, voiding parameters significantly improved in both groups, with no notable inter-group differences. Patients with higher PdetQmax exhibited less advanced remodeling and inflammation. Significant dysregulation of gene expression was observed pre-TURP, partially reversed post-TURP. The transcription factor SOX21 and its target THBS4 demonstrated normalization after TURP.

Their findings revealed a substantial yet incomplete reversal of cell signaling pathways post-TURP, consistent with improved urodynamic parameters. Investigators proposed a set of biomarker genes indicative of BPO and bladder changes. This study sheds light on the progressive stages of obstruction-induced bladder decompensation and offers insights into selecting an optimal intervention point to mitigate contractility loss.

Source: bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01417-8