Deleterious impact of nerve growth factor precursor (proNGF) on bladder urothelial and smooth muscle cells

The nerve growth factor precursor (proNGF) activates p75(NTR) receptor and promotes cell death in different tissues, yet this pathophysiological effect is not fully described in the bladder. The aim of this study was to identify the biological effect of proNGF/p75(NTR) activation on urothelial and smooth muscle (SM) cells of rodents' bladder. Cell viability was assessed by MTT assay which showed a significant reduction in urothelial viability after 24 h of incubation with proNGF in culture medium [5 or 10 nM], an effect not seen in SM cells. Western blot analysis on cellular protein extracts showed increased expression of the transmembrane TNF-alpha and activation of RhoA in urothelial cells exposed to proNGF with no evidence of a nuclear translocation of NF-kappa B assessed by western blotting on nuclear extracts and immunofluorescence. The activation of p75(NTR)-death domain related pathways in urothelial cells such as TNF-alpha or RhoA had a downstream effect on NO release and the junctional protein occludin, as estimated respectively by colorimetric and western blotting. On the other hand, proNGF did not induce TNF-alpha or RhoA expression in SM cells, but induced a significant NF-kappa B nuclear translocation. ProNGF had a different impact on SM as evidenced by a significant doseand time-dependent increase in SM proliferation and migration examined by MTT test and cell migration assay. Together, our results indicate that activation of proNGF/p75(NTR) axis induces degenerative changes to the urothelial layer impacting its barrier and signaling integrity, while promoting adaptive proliferative changes in detrusor SM cells that can interfere with the contractile phenotype essential for proper bladder function.

Automated summary

The activation of proNGF/p75(NTR) axis induces degenerative changes to the urothelial layer impacting its barrier and signaling integrity, while promoting adaptive proliferative changes in detrusor SM cells that can interfere with the contractile phenotype essential for proper bladder function. This study highlights the different effects of proNGF on urothelial and smooth muscle cells in the bladder, suggesting a potential role in bladder dysfunction.