Bulk and single-cell transcriptome profiling identify potential cellular targets of the long noncoding RNA Gas5 in renal fibrosis

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2024-08, Vol.1870 (6), p.167206, Article 167206
• Main Authors: Zhang, Xiang, Hu, Shouci, Xiang, Xiaojun, Li, Zhiyu, Chen, Zhejun, Xia, Cong, He, Qiang, Jin, Juan, Chen, Hongbo
• Format: Article
• Language: English
• Subjects: Differentiation and activation of immune cells; lncRNA Gas5; PPAR signaling; Renal fibrosis; Unilateral ureteral obstruction
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167206

The long noncoding RNA growth arrest-specific 5 (lncRNA Gas5) is implicated in various kidney diseases. In this study, we investigated the lncRNA Gas5 expression profile and its critical role as a potential biomarker in the progression of chronic kidney disease. Subsequently, we assessed the effect of lncRNA Gas5 deletion on renal fibrosis induced by unilateral ureteral obstruction (UUO). The results indicated that loss of lncRNA Gas5 exacerbates UUO-induced renal injury and extracellular matrix deposition. Notably, the deletion of lncRNA Gas5 had a similar effect on control mice. The fibrogenic phenotype observed in mice lacking lncRNA Gas5 correlates with peroxisome proliferator-activated receptor (PPAR) signaling pathway activation and aberrant cytokine and chemokine reprogramming. Single-cell RNA sequencing analysis revealed key transcriptomic features of fibroblasts after Gas5 deletion, revealing heterogeneous cellular states suggestive of a propensity for renal fibrosis. Our findings indicate that lncRNA Gas5 regulates the differentiation and activation of immune cells and the transcription of key genes in the PPAR signaling pathway. These data offer novel insights into the involvement of lncRNA Gas5 in renal fibrosis, potentially paving the way for innovative diagnostic and therapeutic targets. •lncRNA Gas5 is a potential biomarker in chronic kidney disease.•Loss of lncRNA Gas5 exacerbates renal injury and extracellular matrix deposition in UUO-induced renal fibrosis.•We explain the role of lncRNA Gas5 in renal fibrosis based on the integration of scRNA-Seq and Bulk RNA-Seq analysis for the first time.•lncRNA Gas5 could regulate the differentiation and activation of immune cells and transcription of key genes in PPAR signal pathway.