Exploring the therapeutic potential of PACAP in Hunner-type Interstitial Cystitis

Area of Science:

• Urology
• Immunology
• Molecular Biology

Background:

• Hunner-type Interstitial Cystitis (HIC) is a chronic bladder condition characterized by inflammation and fibrosis.
• The precise molecular mechanisms underlying HIC pathogenesis remain incompletely understood.

Purpose of the Study:

• To investigate the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in HIC.
• To evaluate PACAP as a potential therapeutic target for HIC.

Main Methods:

• PACAP expression analysis in HIC patient bladder tissues via immunohistochemistry.
• Establishment of an in vitro HIC model using LPS-stimulated SV-HUC1 cells.
• PACAP knockdown using siRNA to assess effects on inflammatory and fibrotic markers (IL-6, IL-1β, TNF-α, fibronectin 1, TGF-β1, collagen I) using qPCR, Western blot, and ELISA.
• Analysis of cell migration and proliferation using wound healing and CCK-8 assays.
• Transcriptomic profiling to identify differentially expressed genes.

Main Results:

• PACAP expression was significantly upregulated in HIC bladder tissues.
• LPS stimulation increased PACAP, inflammatory cytokines, and fibrotic markers in vitro.
• PACAP knockdown suppressed inflammation and fibrosis, and inhibited cell migration and proliferation.
• Transcriptomic analysis confirmed PACAP's involvement in HIC pathogenesis.

Conclusions:

• PACAP plays a critical role in the inflammatory and fibrotic pathways of HIC.
• Targeting PACAP can alleviate HIC-associated pathological responses.
• PACAP represents a promising novel therapeutic target for HIC.