Human umbilical cord mesenchymal stem cell–derived exosomes are associated with changes in renal injury markers, gut microbiota composition, and inflammatory signaling in IgA nephropathy

BackgroundIgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of end-stage kidney disease, yet disease-specific therapeutic options remain limited. Emerging evidence implicates gut microbiota dysbiosis and innate immune activation, particularly NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome-related signaling, in IgAN pathogenesis.

However, whether human umbilical cord mesenchymal stem cell–derived exosomes (hUCMSC-Exos) are associated with changes in renal injury and gut–immune-related parameters in IgAN remains unclear.MethodshUCMSC-Exos were isolated and administered to an IgAN-like mouse model. Renal function, histopathological changes, and systemic inflammatory markers were assessed.

Gut microbiota composition was analyzed using 16S rRNA sequencing, and exploratory microbial co-occurrence networks were constructed. In vitro, podocytes stimulated with galactose-deficient IgA1 (Gd-IgA1) were used to evaluate inflammasome-related markers following exosome exposure.

Transcriptomic data from human IgAN glomeruli (GSE93798) were analyzed to explore inflammatory and immune-related gene signatures.ResultshUCMSC-Exos were associated with changes in renal injury markers in IgAN-like mice, along with alterations in gut microbial composition.