Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction

Area of Science:

• Cell Biology
• Urology
• Pediatrics

Background:

• Neurogenic lower urinary tract dysfunction (NLUTD) causes significant bladder smooth muscle cell (SMC) remodeling.
• The role of autophagy in pediatric NLUTD-associated SMC changes is not well understood.

Purpose of the Study:

• To investigate the role of autophagy in bladder smooth muscle cell remodeling in pediatric patients with NLUTD.
• To explore potential therapeutic targets for managing NLUTD.

Main Methods:

• Bladder biopsies from children with NLUTD and healthy controls were analyzed.
• Immunohistochemistry was used to assess SMC markers (calponin, smoothelin) and autophagy proteins (LC3, ATG5, Beclin1).
• Contractile function of bladder-derived SMCs was evaluated.

Main Results:

• ATG5 gene and protein expression were upregulated in NLUTD bladder tissue.
• Accumulation of autophagosomes (indicated by LC3 puncta) was observed in NLUTD SMCs.
• Elevated ATG5 in NLUTD was associated with decreased expression of contractile proteins (smoothelin, calponin).
• Pharmacological inhibition of autophagy halted normal SMC growth and reduced elevated ATG5 in NLUTD SMCs.

Conclusions:

• Autophagy plays a crucial role in the remodeling and functional alterations of bladder smooth muscle in pediatric NLUTD.
• Targeting autophagy pathways could lead to novel therapeutic interventions for preventing NLUTD progression.