Background: Type IV lupus nephritis (LNIV) is a severe disease characterized by diffuse proliferative lesions, and its prognosis is worse with cellular crescent (LNIV-CC) involvement. Urinary exosomes have been shown to reflect the degree of kidney injury. This study was aimed to identify non-invasive diagnostic markers for LNIV-CC. We analysed the expression profile of microRNAs (miRNAs) isolated from urinary exosomes in patients with LNIV-CC and LNIV, and healthy individuals using high-throughput sequencing.
Results: A total of 66 differentially expressed miRNAs were identified, which were significantly enriched in 15 signalling pathways. Bioinformatic analysis revealed a co-expression network of miRNAs, predicted transcription factors and target mRNAs. Expression of three miRNAs including miR-3135b, miR-654-5p, and miR-146a-5p were further analysed and validated by reverse transcription-quantitative polymerase chain reaction. ROC analysis suggested these as candidate biomarkers for LNIV-CC.
Conclusions: LNIV-CC has a unique miRNA expression profile of urinary exosome and complex regulatory network. miR-3135b, miR-654-5p and miR-146a-5p in urinary exosomes could be used as novel non-invasive diagnostic markers for LNIV-CC.
Keywords: High-throughput sequencing; Type IV lupus nephritis; Urinary exosome; miRNAs.