The TGF-β1 pathway is early involved in neurogenic bladder fibrosis of juvenile rats
PEDIATRIC RESEARCH(2021)
Abstract
Background This study investigated whole neurogenic bladder’s progression changes, as well as the expression of TGF-β1 fibrosis pathway-related proteins in bilateral spinal nerve-amputated juvenile rats. Methods Sixty-four 8-week-old rats (32 bilateral L6 + S1 spinal nerve amputated and 32 sham operated) were selected. Cystometry was performed. General assessments, Masson, Sirius red, immunohistochemical staining, and western blotting of fibrosis and TGF-β1 pathway-related proteins were conducted using bladder tissues. Results Cystometry results showed that the basal intravesical pressures and bladder capacities in nerve-amputated rats were significantly higher than those in sham-operated ones. Compared to the sham-operated groups, the bladder size and wall thickness in the nerve-amputated groups increased initially but then decreased over time. However, bladder weight continuously increased over time. Disintegration, thickening, and hypertrophy of the bladder wall were found over time in the amputated rats. Moreover, there was a significant increase in collagen III, and the ratio of collagen III/I was higher in amputated rats ( P < 0.01). Finally, the expression of TGF-β1, TGF-βRI, Smad2, and collagen III and I increased in amputated bladder tissues, while Smad6 decreased over time. Conclusions The main clinical features of pediatric neurogenic bladder (PNB) were detrusor paralysis and continuous intravesical pressure. Biological molecular findings are earlier than the pathophysiological findings. Therefore, early preventing bladder fibrosis by targeting TGF-β1/Smad pathway-related proteins once knowing the PNB diagnosis might be an alternative treatment for PNB. Impact The study found that the main clinical features of PNB were detrusor paralysis, continuous intravesical pressure, and increased TGF-beta/Smad signal proteins over time. The study makes contributions to the literature because it suggests biological molecular findings are earlier than the pathophysiological findings by various staining in PNB. The study investigated whole neurogenic bladder’s progression changes, as well as the expression of TGF-β1 fibrosis pathway-related proteins in the spinal nerve-injured PNB juvenile rat models, which suggests that early prevention of bladder fibrosis by targeting TGF-β1/Smad pathway-related proteins once knowing the PNB diagnosis might be an alternative treatment for pediatric neurogenic bladder.
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Key words
Medicine/Public Health,general,Pediatrics,Pediatric Surgery
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