Artesunate remarkably alleviates interstitial cystitis/bladder pain syndrome in a murine model: Novel molecular signature deciphered by bulk tissue and single-cell transcriptomic analysis.

Interstitial cystitis/bladder pain syndrome is a chronic pain syndrome of elusive etiology, accompanied by lower urinary tract symptoms. Over the past decades, many studies have been carried out for exploration of more effective therapies against IC/BPS. However, the results have been inconsistent, probably due to the multifactorial nature of IC/BPS. We establish a model of IC/BPS in mice by combining protamine sulfate /lipopolysaccharide and phenylephrine. Typical histological changes and symptoms were observed. We then explored the effectiveness of artesunate (ART), which has been reported to alleviate autoimmune diseases. Phenotypic tests demonstrated a significant reduction in symptoms. Histological staining showed pathological improvement. WGCNA identified three gene modules specifically related to IC/BPS, and six genes were identified as hub genes. CIBERSORT analysis showed that the activated NK cells seem to be decreased in IC modeling group and partially restored in IC + ART group, whereas the resting NK cells showed the opposite trend. Single-cell transcriptomic analysis elaborated on the changing trends of subgroups of infiltrated immune cells, including T cells, NK cells, and dendritic cells. Our study represents our effort in establishing a reliable and reproducible IC/BPS murine model, and the first study using scRNA-seq in exploring the immune microenvironment of the IC/BPS murine model, and the possible molecular mechanisms of ART treatment in IC/BPS. Further studies are needed to confirm the effect of ART in IC/BPS patients.